| 1980 regular season game log: 93–70 (Home: 55–26; Away: 38–44)[7] |
April: 13–5 (Home: 9–3; Away: 4–2)
| # | Date | Time (CT) | Opponent | Score | Win | Loss | Save | Time of Game | Attendance | Record | Box/ Streak |
| 1 | April 10 | 7:35 p.m. CST | Dodgers | W 3–2 | Richard (1–0) | Hooton (0–1) | Sambito (1) | 2:03 | 33,270 | 1–0 | W1 |
| 2 | April 11 | 7:35 p.m. CST | Dodgers | W 10–6 | Smith (1–0) | Stanhouse (0–1) | – | 2:58 | 30,701 | 2–0 | W2 |
| 3 | April 12 | 3:15 p.m. CST | Dodgers | L 5–6 (17) | Howe (1–0) | Smith (1–1) | Hooton (1) | 5:35 | 24,609 | 2–1 | L1 |
| 4 | April 13 | 2:05 p.m. CST | Dodgers | W 4–2 | Forsch (1–0) | Goltz (0–1) | LaCorte (1) | 2:19 | 33,676 | 3–1 | W1 |
| 5 | April 14 | 7:35 p.m. CST | Braves | W 5–4 | Sambito (1–0) | Garber (0–1) | – | 3:15 | 15,017 | 4–1 | W2 |
| 6 | April 15 | 7:35 p.m. CST | Braves | W 6–2 | Niekro (1–0) | McWilliams (0–2) | – | 2:14 | 15,712 | 5–1 | W3 |
| 7 | April 17 | 3:00 p.m. CST | @ Dodgers | L 4–6 | Reuss (1–0) | Smith (1–2) | – | 3:06 | 45,476 | 5–2 | L1 |
| 8 | April 18 | 9:30 p.m. CST | @ Dodgers | W 7–4 | Forsch (2–0) | Goltz (0–2) | Andújar (1) | 3:20 | 41,112 | 6–2 | W1 |
| 9 | April 19 | 9:00 p.m. CST | @ Dodgers | W 2–0 | Richard (2–0) | Welch (0–1) | – | 2:40 | 50,112 | 7–2 | W2 |
| 10 | April 20 | 3:00 p.m. CST | @ Dodgers | L 2–4 | Reuss (2–0) | Niekro (1–1) | – | 2:27 | 39,442 | 7–3 | L1 |
| 11 | April 21 | 7:35 p.m. CST | Reds | L 5–6 | LaCoss (3–0) | Ruhle (0–1) | Hume (3) | 3:09 | 29,067 | 7–4 | L2 |
| 12 | April 22 | 7:35 p.m. CST | Reds | W 8–0 | Ryan (1–0) | Pastore (2–1) | – | 2:45 | 30,094 | 8–4 | W1 |
| 13 | April 23 | 7:35 p.m. CST | Reds | L 2–3 (12) | Hume (2–0) | Andújar (0–1) | Bair (1) | 3:39 | 29,828 | 8–5 | L1 |
| 14 | April 25 | 7:35 p.m. CST | Mets | W 7–4 | Richard (3–0) | Falcone (1–1) | – | 2:52 | 24,140 | 9–5 | W1 |
| 15 | April 26 | 7:35 p.m. CST | Mets | W 6–0 | Niekro (2–1) | Glynn (0–1) | LaCorte (2) | 2:42 | 44,540 | 10–5 | W2 |
| 16 | April 27 | 2:05 p.m. CDT | Mets | W 4–3 (12) | LaCorte (1–0) | Allen (0–3) | – | 3:37 | 20,828 | 11–5 | W3 |
| 17 | April 29 | 7:05 p.m. CDT | @ Reds | W 3–0 | Forsch (3–0) | Leibrandt (1–2) | – | 2:14 | 18,092 | 12–5 | W4 |
| 18 | April 30 | 7:05 p.m. CDT | @ Reds | W 5–1 | Richard (4–0) | Seaver (1–1) | – | 2:21 | 19,821 | 13–5 | W5 |
|
May: 12–14 (Home: 4–4; Away: 8–10)
| # | Date | Time (CT) | Opponent | Score | Win | Loss | Save | Time of Game | Attendance | Record | Box/ Streak |
| 19 | May 1 | 7:05 p.m. CDT | @ Reds | W 9–3 | Niekro (3–1) | LaCoss (3–2) | – | 3:00 | 18,215 | 14–5 | W6 |
| 20 | May 2 | 7:38 p.m. CDT | @ Cardinals | L 1–9 | Hood (1–1) | Ryan (1–1) | Kaat (1) | 2:39 | 23,009 | 14–6 | L1 |
| 21 | May 3 | 7:10 p.m. CDT | @ Cardinals | W 4–2 | Ruhle (1–1) | Martínez (1–2) | Sambito (2) | 2:10 | 23,292 | 15–6 | W1 |
| 22 | May 4 | 1:19 p.m. CDT | @ Cardinals | W 4–2 | Forsch (4–0) | Sykes (1–3) | LaCorte (3) | 2:37 | 17,262 | 16–6 | W2 |
| 23 | May 5 | 12:35 p.m. CDT | @ Expos | L 1–10 | Palmer (1–0) | Richard (4–1) | – | 2:41 | 5,477 | 16–7 | L1 |
| 24 | May 6 | 12:35 p.m. CDT | @ Expos | W 8–4 | Niekro (4–1) | Grimsley (1–2) | – | 2:33 | 5,503 | 17–7 | W1 |
| 25 | May 7 | 12:35 p.m. CDT | @ Expos | L 0–3 | Sanderson (2–2) | Ryan (1–2) | Fryman (3) | 2:29 | 7,386 | 17–8 | L1 |
| 26 | May 9 | 6:35 p.m. CDT | @ Braves | L 4–5 | McWilliams (2–2) | Forsch (4–1) | Bradford (1) | 2:21 | 11,111 | 17–9 | L2 |
| 27 | May 10 | 6:35 p.m. CDT | @ Braves | W 3–2 (11) | LaCorte (2–0) | Garber (1–2) | Sambito (3) | 3:15 | 13,798 | 18–9 | W1 |
| 28 | May 11 | 1:15 p.m. CDT | @ Braves | L 4–7 | Niekro (2–4) | Niekro (4–2) | – | 2:25 | 10,871 | 18–10 | L1 |
| 29 | May 13 | 7:35 p.m. CDT | Expos | L 2–3 | Palmer (2–0) | Ryan (1–3) | – | 2:42 | 24,835 | 18–11 | L2 |
| 30 | May 14 | 7:35 p.m. CDT | Expos | L 0–1 | Sanderson (3–2) | Forsch (4–2) | Fryman (5) | 2:19 | 20,636 | 18–12 | L3 |
| 31 | | 7:35 p.m. CDT | Phillies | L 0–3 | Ruthven (4–2) | Richard (4–2) | — | 2:06 | 33,610 | 18–13 | L4 |
| 32 | | 7:35 p.m. CDT | Phillies | L 2–4 | Christenson (3–0) | Niekro (4–3) | Noles (3) | 2:25 | 43,525 | 18–14 | L5 |
| 33 | | 2:05 p.m. CDT | Phillies | W 3–0 | Ryan (2–3) | Lerch (2–3) | — | 2:07 | 33,950 | 19–14 | W1 |
| 34 | May 20 | 7:05 p.m. CDT | @ Mets | W 3–2 | Forsch (5–2) | Swan (2–3) | – | 2:29 | 8,466 | 20–14 | W2 |
| 35 | May 21 | 7:05 p.m. CDT | @ Mets | L 1–5 | Falcone (3–2) | Richard (4–3) | Allen (7) | 2:37 | 4,233 | 20–15 | L1 |
| 36 | May 22 | 7:05 p.m. CDT | @ Mets | W 8–5 | Niekro (5–3) | Kobel (0–4) | LaCorte (4) | 2:55 | 7,812 | 21–15 | W1 |
| 37 | | 7:05 p.m. CDT | @ Phillies | L 0–3 | Carlton (8–2) | Ryan (2–4) | — | 2:11 | 27,822 | 21–16 | L1 |
| 38 | | 6:05 p.m. CDT | @ Phillies | L 4–5 | Saucier (2–3) | Andújar (0–2) | McGraw (3) | 2:28 | 28,539 | 21–17 | L2 |
| 39 | | 12:35 p.m. CDT | @ Phillies | L 2–6 | Ruthven (5–3) | Forsch (5–3) | — | 2:10 | 37,340 | 21–18 | L3 |
| 40 | May 26 | 7:35 p.m. CDT | Padres | W 4–1 | Richard (5–3) | Curtis (3–4) | Sambito (4) | 2:59 | 18,242 | 22–18 | W1 |
| 41 | May 27 | 7:35 p.m. CDT | Padres | W 4–3 | LaCorte (3–0) | Fingers (5–5) | – | 2:47 | 18,246 | 23–18 | W2 |
| 42 | May 28 | 7:35 p.m. CDT | Padres | W 1–0 | Ryan (3–4) | Wise (2–3) | – | 2:30 | 19,697 | 24–18 | W3 |
| 43 | May 30 | 9:38 p.m. CDT | @ Giants | L 2–3 | Blue (8–2) | Forsch (5–4) | – | 2:19 | 10,511 | 24–19 | L1 |
| 44 | May 31 | 3:09 p.m. CDT | @ Giants | W 5–0 | Richard (6–3) | Montefusco (2–4) | – | 2:15 | 11,649 | 25–19 | W1 |
|
June: 18–9 (Home: 13–4; Away: 5–5)
| # | Date | Time (CT) | Opponent | Score | Win | Loss | Save | Time of Game | Attendance | Record | Box/ Streak |
| 45 | June 1 | 3:09 p.m. CDT | @ Giants | L 2–6 | Knepper (4–6) | Niekro (5–4) | – | 2:35 | 19,801 | 25–20 | L1 |
| 46 | June 2 | 9:00 p.m. CDT | @ Padres | L 0–3 | Wise (3–3) | Ryan (3–5) | Rasmussen (1) | 2:16 | 27,176 | 25–21 | L2 |
| 47 | June 3 | 9:00 p.m. CDT | @ Padres | W 3–2 | Ruhle (2–1) | Jones (4–4) | LaCorte (5) | 2:20 | 12,363 | 26–21 | W1 |
| 48 | June 4 | 9:00 p.m. CDT | @ Padres | W 4–3 | Forsch (6–4) | Fingers (5–6) | Sambito (5) | 2:27 | 13,619 | 27–21 | W2 |
| 49 | June 6 | 7:35 p.m. CDT | Giants | W 2–0 | Richard (7–3) | Knepper (4–7) | – | 2:02 | 26,822 | 28–21 | W3 |
| 50 | June 7 | 7:35 p.m. CDT | Giants | W 3–0 | Niekro (6–4) | Whitson (2–7) | – | 2:05 | 42,263 | 29–21 | W4 |
| 51 | June 8 | 7:35 p.m. CDT | Giants | W 5–4 | Sambito (2–0) | Minton (2–3) | – | 2:30 | 28,327 | 30–21 | W5 |
| 52 | June 9 | 7:35 p.m. CDT | Cubs | W 6–2 | Forsch (7–4) | Lamp (6–2) | – | 2:31 | 19,022 | 31–21 | W6 |
| 53 | June 10 | 7:35 p.m. CDT | Cubs | W 5–2 | Ruhle (3–1) | Krukow (3–7) | – | 2:22 | 21,201 | 32–21 | W7 |
| 54 | June 11 | 7:35 p.m. CDT | Cubs | W 3–0 | Richard (8–3) | Reuschel (5–6) | – | 2:18 | 31,599 | 33–21 | W8 |
| – | June 12 | | Cubs | Postponed (Schedule change) (Makeup date: June 9) |
| 55 | June 13 | 6:35 p.m. CDT | @ Pirates | L 3–5 | Solomon (4–0) | Niekro (6–5) | Tekulve (9) | 2:35 | 31,854 | 33–22 | L1 |
| 56 | June 14 | 6:05 p.m. CDT | @ Pirates | W 7–3 | Ryan (4–5) | Robinson (2–2) | LaCorte (6) | 3:08 | 33,922 | 34–22 | W1 |
| 57 | June 15 | 12:35 p.m. CDT | @ Pirates | L 1–4 | Candelaria (4–5) | Forsch (7–5) | – | 2:08 | 49,541 | 34–23 | L1 |
| 58 | June 16 | 1:30 p.m. CDT | @ Cubs | W 2–1 | Ruhle (4–1) | Hernández (1–5) | Smith (1) | 2:35 | 15,289 | 35–23 | W1 |
| 59 | June 17 | 1:30 p.m. CDT | @ Cubs | W 7–1 | Richard (9–3) | McGlothen (3–4) | Andújar (2) | 2:54 | 19,480 | 36–23 | W2 |
| 60 | June 18 | 7:35 p.m. CDT | Cardinals | W 3–0 | Niekro (7–5) | Kaat (1–4) | – | 2:08 | 24,459 | 37–23 | W3 |
| 61 | June 19 | 7:35 p.m. CDT | Cardinals | W 2–0 | Ryan (5–5) | Sykes (1–6) | Sambito (6) | 2:02 | 24,663 | 38–23 | W4 |
| 62 | June 20 | 7:35 p.m. CDT | Pirates | W 6–4 | Forsch (8–5) | Candelaria (4–6) | Sambito (7) | 2:14 | 35,955 | 39–23 | W5 |
| 63 | June 21 | 7:35 p.m. CDT | Pirates | W 4–2 | Ruhle (5–1) | Blyleven (2–7) | Sambito (8) | 2:30 | 45,867 | 40–23 | W6 |
| 64 | June 22 | 7:35 p.m. CDT | Pirates | L 1–2 | Bibby (8–1) | Niekro (7–6) | Jackson (3) | 2:33 | 46,213 | 40–24 | L1 |
| 65 | June 23 | 7:35 p.m. CDT | Dodgers | L 0–3 | Sutcliffe (2–4) | Andújar (0–3) | – | 2:29 | 29,753 | 40–25 | L2 |
| 66 | June 24 | 7:35 p.m. CDT | Dodgers | W 5–4 (12) | LaCorte (4–0) | Beckwith (3–1) | – | 4:13 | 34,388 | 41–25 | W1 |
| 67 | June 25 | 7:35 p.m. CDT | Dodgers | L 2–9 | Welch (8–2) | Forsch (8–6) | – | 2:50 | 34,416 | 41–26 | L1 |
| 68 | June 27 | 7:35 p.m. CDT | Reds | W 5–4 | Niekro (8–6) | Pastore (9–4) | Sambito (9) | 2:31 | 36,648 | 42–26 | W1 |
| 69 | June 28 | 7:35 p.m. CDT | Reds | L 5–8 | Price (1–0) | Richard (9–4) | Hume (11) | 3:08 | 44,025 | 42–27 | L1 |
| 70 | June 29 | 5:00 p.m. CDT | Reds | W 12–10 | LaCorte (5–0) | Soto (0–3) | Sambito (10) | 3:20 | 38,408 | 43–27 | W1 |
| 71 | June 30 | 6:35 p.m. CDT | @ Braves | L 4–5 (11) | Hrabosky (4–1) | Sambito (2–1) | – | 2:53 | 8,208 | 43–28 | L1 |
|
July: 13–16 (Home: 8–6; Away: 5–10)
| # | Date | Time (CT) | Opponent | Score | Win | Loss | Save | Time of Game | Attendance | Record | Box/ Streak |
| 72 | July 1 | 6:35 p.m. CDT | @ Braves | L 4–13 | Alexander (6–3) | Niekro (8–7) | – | 2:47 | 9,546 | 43–29 | L2 |
| 73 | July 2 | 6:35 p.m. CDT | @ Braves | L 0–14 | Niekro (6–10) | Ruhle (5–2) | – | 2:27 | 21,908 | 43–30 | L3 |
| 74 | July 3 | 6:35 p.m. CDT | @ Braves | W 4–3 | Richard (10–4) | Boggs (3–4) | LaCorte (7) | 2:44 | 15,769 | 44–30 | W1 |
| 75 | July 4 | 7:05 p.m. CDT | @ Reds | L 1–8 | Leibrandt (8–4) | Ryan (5–6) | – | 2:42 | 37,047 | 44–31 | L1 |
| 76 | July 5 (1) | 4:37 p.m. CDT | @ Reds | L 6–8 | Soto (1–3) | Forsch (8–7) | – | 2:46 | N/A | 44–32 | L2 |
| 77 | July 5 (2) | 7:58 p.m. CDT | @ Reds | L 2–3 | LaCoss (5–7) | Andújar (0–4) | Hume (12) | 2:34 | 44,083 | 44–33 | L3 |
| 78 | July 6 | 1:15 p.m. CDT | @ Reds | W 3–2 | Niekro (9–7) | Pastore (10–5) | LaCorte (8) | 2:37 | 30,045 | 45–33 | W1 |
| — | | 7:40 p.m. CDT | 51st All-Star Game in Los Angeles, CA |
| 79 | July 10 | 9:30 p.m. CDT | @ Dodgers | L 3–4 | Howe (3–4) | Ryan (5–7) | – | 2:52 | 49,692 | 45–34 | L1 |
| 80 | July 11 | 7:10 p.m. CDT | @ Dodgers | L 2–3 | Reuss (10–2) | Forsch (8–8) | Howe (8) | 2:30 | 42,754 | 45–35 | L2 |
| 81 | July 12 | 7:35 p.m. CDT | Braves | W 9–5 | Niekro (10–8) | McWilliams (5–6) | Smith (2) | 2:54 | 38,610 | 46–35 | W1 |
| 82 | July 13 (1) | 5:35 p.m. CDT | Braves | W 6–5 | Sambito (3–1) | Garber (2–5) | LaCorte (9) | 2:48 | N/A | 47–35 | W2 |
| 83 | July 13 (2) | 8:58 p.m. CDT | Braves | W 6–1 | Ruhle (6–2) | Boggs (3–5) | – | 2:28 | 31,230 | 48–35 | W3 |
| 84 | July 14 | 7:35 p.m. CDT | Braves | L 0–2 | Niekro (7–11) | Pladson (0–1) | – | 2:19 | 20,247 | 48–36 | L1 |
| 85 | | 7:35 p.m. CDT | Phillies | W 3–2 | Sambito (4–1) | Ruthven (8–6) | — | 2:08 | 24,223 | 49–36 | W1 |
| 86 | | 7:35 p.m. CDT | Phillies | L 2–4 | Walk (6–0) | Forsch (8–9) | — | 2:06 | 28,532 | 49–37 | L1 |
| 87 | | 7:35 p.m. CDT | Phillies | L 1–2 | Carlton (15–4) | Niekro (10–8) | — | 2:18 | 26,403 | 49–38 | L2 |
| 88 | July 18 | 7:35 p.m. CDT | Expos | L 4–5 (11) | Fryman (4–4) | Smith (1–3) | Norman (4) | 3:24 | 26,389 | 49–39 | L3 |
| 89 | July 19 (1) | 5:35 p.m. CDT | Expos | W 4–2 | Andújar (1–4) | Lea (2–4) | Smith (3) | 2:44 | 40,499 | 50–39 | W1 |
| 90 | July 19 (2) | 8:54 p.m. CDT | Expos | L 2–5 | Gullickson (1–2) | Pladson (0–2) | – | 2:35 | 39,507 | 50–40 | L1 |
| 91 | July 20 | 7:35 p.m. CDT | Expos | W 4–3 | Sambito (5–1) | Norman (0–1) | – | 2:16 | 28,513 | 51–40 | W1 |
| 92 | July 21 | 7:35 p.m. CDT | Mets | W 3–2 | LaCorte (6–1) | Allen (4–6) | – | 2:23 | 20,548 | 52–40 | W2 |
| 93 | July 22 | 7:35 p.m. CDT | Mets | W 6–5 | Roberge (1–0) | Glynn (3–3) | Smith (4) | 3:02 | 26,815 | 53–40 | W3 |
| 94 | July 23 | 7:35 p.m. CDT | Mets | L 3–4 | Reardon (5–5) | LaCorte (6–1) | Allen (16) | 2:44 | 30,236 | 53–41 | L1 |
| 95 | July 25 | 6:35 p.m. CDT | @ Expos | W 9–8 | LaCorte (7–1) | Sosa (5–4) | – | 3:31 | 50,217 | 54–41 | W1 |
| 96 | July 26 | 6:35 p.m. CDT | @ Expos | L 1–2 (12) | Sahnsen (7–4) | LaCorte (7–2) | – | 3:46 | 42,400 | 54–42 | L1 |
| 97 | July 27 | 12:35 p.m. CDT | @ Expos | W 6–3 | Niekro (11–8) | Lee (3–5) | Smith (5) | 3:02 | 41,107 | 55–42 | W1 |
| 98 | | 6:35 p.m. CDT | @ Phillies | W 3–2 (10) | Sambito (6–1) | Reed (6–4) | — | 2:41 | 30,181 | 56–42 | W2 |
| 99 | | 6:35 p.m. CDT | @ Phillies | L 6–9 | Saucier (5–3) | LaCorte (7–3) | McGraw (8) | 3:05 | 30,252 | 56–43 | L1 |
| 100 | | 6:35 p.m. CDT | @ Phillies | L 4–6 | Ruthven (10–7) | Ryan (5–8) | McGraw (9) | 2:36 | 31,342 | 56–44 | L2 |
|
August: 18–12 (Home: 9–4; Away: 9–8)
| # | Date | Time (CT) | Opponent | Score | Win | Loss | Save | Time of Game | Attendance | Record | Box/ Streak |
| 101 | August 1 | 7:05 p.m. CDT | @ Mets | L 4–5 | Reardon (6–5) | Smith (1–4) | – | 2:42 | 16,612 | 56–45 | L3 |
| 102 | August 2 | 6:05 p.m. CDT | @ Mets | L 3–5 | Allen (5–6) | Niekro (11–9) | – | 2:46 | 45,426 | 56–46 | L4 |
| 103 | August 3 | 1:05 p.m. CDT | @ Mets | W 3–2 (10) | Sambito (7–1) | Reardon (6–6) | – | 3:41 | 22,492 | 57–46 | W1 |
| 104 | August 4 | 7:35 p.m. CDT | Giants | W 4–2 | Ryan (6–8) | Hargesheimer (2–1) | Sambito (11) | 2:19 | 33,884 | 58–46 | W2 |
| 105 | August 5 | 7:35 p.m. CDT | Giants | L 3–9 | Lavelle (5–5) | Pladson (0–3) | – | 3:03 | 24,198 | 58–47 | L1 |
| 106 | August 6 | 7:35 p.m. CDT | Giants | W 1–0 | Forsch (9–9) | Blue (9–6) | – | 2:10 | 23,478 | 59–47 | W1 |
| 107 | August 7 | 7:35 p.m. CDT | Padres | L 1–5 | Shirley (9–7) | Niekro (11–10) | – | 2:59 | 20,044 | 59–48 | L1 |
| 108 | August 8 | 7:35 p.m. CDT | Padres | L 3–5 | Eichelberger (3–0) | Sambito (7–2) | Fingers (15) | 2:45 | 15,207 | 59–49 | L2 |
| 109 | August 9 | 7:35 p.m. CDT | Padres | W 9–5 | Smith (2–4) | D'Acquisto (2–3) | – | 2:50 | 21,233 | 60–49 | W1 |
| 110 | August 10 | 2:05 p.m. CDT | Padres | L 2–3 | Wise (4–5) | Sambito (7–3) | – | 2:21 | 20,514 | 60–50 | L1 |
| 111 | August 11 | 9:35 p.m. CDT | @ Giants | L 4–5 | Blue (10–6) | Forsch (9–10) | Minton (12) | 2:48 | 10,755 | 60–51 | L2 |
| 112 | August 12 | 9:35 p.m. CDT | @ Giants | L 0–2 | Ripley (6–5) | Niekro (11–11) | Lavelle (6) | 2:05 | 29,770 | 60–52 | L3 |
| 113 | August 13 | 2:05 p.m. CDT | @ Giants | L 5–6 (12) | Rowland (1–0) | Smith (2–5) | – | 3:42 | 10,149 | 60–53 | L4 |
| 114 | August 14 | 3:00 p.m. CDT | @ Padres | W 2–1 | Ryan (7–8) | Curtis (4–8) | – | 2:18 | 12,150 | 61–53 | W1 |
| 115 | August 15 | 9:00 p.m. CDT | @ Padres | W 3–1 (20) | Smith (3–5) | Rasmussen (2–9) | – | 6:17 | 14,177 | 62–53 | W2 |
| 116 | August 17 (1) | 3:00 p.m. CDT | @ Padres | W 5–0 | Forsch (10–10) | Jones (5–12) | – | 2:06 | N/A | 63–53 | W3 |
| 117 | August 17 (2) | 5:41 p.m. CDT | @ Padres | W 9–2 | Niekro (12–11) | Mura (4–5) | – | 2:23 | 16,120 | 64–53 | W4 |
| 118 | August 19 | 7:35 p.m. CDT | Pirates | W 5–2 | Ryan (8–8) | Candelaria (8–13) | Sambito (12) | 2:23 | 39,415 | 65–53 | W5 |
| 119 | August 20 | 7:35 p.m. CDT | Pirates | W 5–1 | Ruhle (7–2) | Bibby (15–3) | Smith (6) | 2:54 | 32,112 | 66–53 | W6 |
| 120 | August 21 | 7:35 p.m. CDT | Pirates | W 12–5 | Sambito (8–3) | Blyleven (7–9) | – | 2:59 | 33,884 | 67–53 | W7 |
| 121 | August 22 | 7:35 p.m. CDT | Cubs | W 3–2 (12) | LaCorte (8–3) | Caudill (1–3) | – | 3:24 | 34,118 | 68–53 | W8 |
| 122 | August 23 | 7:35 p.m. CDT | Cubs | W 1–0 (17) | Niekro (13–11) | Riley (0–4) | – | 4:47 | 25,031 | 69–53 | W9 |
| 123 | August 24 | 7:35 p.m. CDT | Cubs | W 2–1 | Ryan (9–8) | Caudill (1–4) | – | 2:22 | 25,703 | 70–53 | W10 |
| 124 | August 25 | 7:38 p.m. CDT | @ Cardinals | L 1–3 | Hood (3–5) | Ruhle (7–3) | – | 2:16 | 9,185 | 70–54 | L1 |
| 125 | August 26 | 7:37 p.m. CDT | @ Cardinals | W 7–2 | Niekro (14–11) | Kaat (5–6) | – | 2:18 | 10,859 | 71–54 | W1 |
| 126 | August 27 | 7:37 p.m. CDT | @ Cardinals | L 2–10 | Martin (1–0) | Forsch (10–11) | – | 2:41 | 10,025 | 71–55 | L1 |
| 127 | August 28 | 1:30 p.m. CDT | @ Cubs | W 4–1 | Andújar (2–4) | Lamp (10–10) | Sambito (13) | 2:47 | 18,694 | 72–55 | W1 |
| 128 | August 29 | 1:30 p.m. CDT | @ Cubs | W 6–5 | Smith (4–5) | Tidrow (5–5) | LaCorte (10) | 2:49 | 9,994 | 73–55 | W2 |
| 129 | August 30 | 1:15 p.m. CDT | @ Cubs | W 2–0 | Ruhle (8–3) | McGlothen (9–10) | – | 2:47 | 18,803 | 74–55 | W3 |
| 130 | August 31 | 1:15 p.m. CDT | @ Cubs | L 7–8 | Tidrow (6–5) | LaCorte (8–4) | – | 3:00 | 14,823 | 74–56 | L1 |
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September: 16–11 (Home: 10–5; Away: 6–6)
| # | Date | Time (CT) | Opponent | Score | Win | Loss | Save | Time of Game | Attendance | Record | Box/ Streak |
| 131 | September 1 (1) | 10:00 a.m. CDT | @ Pirates | W 10–4 | Smith (5–5) | Robinson (5–8) | – | 3:07 | N/A | 75–56 | W1 |
| 132 | September 1 (2) | 2:42 p.m. CDT | @ Pirates | L 5–7 | Rhoden (5–4) | Pladson (0–4) | Jackson (8) | 2:57 | 26,374 | 75–57 | L1 |
| 133 | September 3 | 6:35 p.m. CDT | @ Pirates | L 4–10 | Candelaria (10–13) | Andújar (2–5) | Romo (9) | 3:00 | 18,502 | 75–58 | L2 |
| 134 | September 5 | 7:40 p.m. CDT | Cardinals | L 5–7 | Seaman (3–1) | Sambito (8–4) | Frazier (2) | 3:15 | 19,628 | 75–59 | L3 |
| 135 | September 6 (1) | 5:38 p.m. CDT | Cardinals | W 9–5 | Niekro (15–11) | Sykes (6–10) | Niemann (1) | 2:40 | N/A | 76–59 | W1 |
| 136 | September 6 (2) | 8:49 p.m. CDT | Cardinals | W 6–4 | Ruhle (9–3) | Martin (1–1) | – | 2:02 | 34,350 | 77–59 | W2 |
| 137 | September 7 | 6:09 p.m. CDT | Cardinals | L 0–2 | Vuckovich (10–9) | Forsch (10–12) | – | 2:00 | 16,475 | 77–60 | L1 |
| 138 | September 9 | 7:35 p.m. CDT | Dodgers | W 5–4 | Smith (6–5) | Howe (6–7) | Sambito (14) | 3:06 | 34,546 | 78–60 | W1 |
| 139 | September 10 | 7:35 p.m. CDT | Dodgers | W 6–5 (12) | Roberge (2–0) | Sutcliffe (3–9) | – | 3:49 | 37,632 | 79–60 | W2 |
| 140 | September 12 | 7:35 p.m. CDT | Giants | W 5–3 | Niekro (16–11) | Whitson (9–11) | Smith (7) | 2:35 | 23,380 | 80–60 | W3 |
| 141 | September 13 | 7:35 p.m. CDT | Giants | W 3–2 | Forsch (11–12) | Blue (13–8) | – | 2:10 | 32,526 | 81–60 | W4 |
| 142 | September 14 | 6:05 p.m. CDT | Giants | W 6–4 | Andújar (3–5) | Montefusco (4–8) | Sambito (15) | 2:43 | 18,471 | 82–60 | W5 |
| 143 | September 15 | 7:35 p.m. CDT | Padres | L 3–6 | Shirley (11–10) | Ryan (9–9) | – | 2:30 | 9,578 | 82–61 | L1 |
| 144 | September 16 | 7:35 p.m. CDT | Padres | L 3–4 | Curtis (8–8) | Ruhle (9–4) | Fingers (21) | 2:57 | 20,383 | 82–62 | L2 |
| 145 | September 17 | 7:05 p.m. CDT | @ Reds | L 0–7 | Soto (10–6) | Niekro (16–12) | – | 2:37 | 25,092 | 82–63 | L3 |
| 146 | September 18 | 11:30 a.m. CDT | @ Reds | W 10–2 | Forsch (12–12) | Pastore (11–7) | Sambito (16) | 2:37 | 23,861 | 83–63 | W1 |
| 147 | September 19 | 9:40 p.m. CDT | @ Giants | L 3–4 | Griffin (1–4) | Andújar (3–6) | Holland (6) | 2:45 | 4,377 | 83–64 | L1 |
| 148 | September 20 | 3:07 p.m. CDT | @ Giants | W 3–2 | Smith (7–5) | Lavelle (6–7) | Sambito (17) | 2:53 | 16,770 | 84–64 | W1 |
| 149 | September 21 | 12:23 p.m. CDT | @ Giants | W 5–1 | Ruhle (10–4) | Blue (14–9) | – | 2:29 | 19,844 | 85–64 | W2 |
| 150 | September 22 | 9:00 p.m. CDT | @ Padres | W 4–2 | Niekro (17–12) | Shirley (11–11) | – | 2:40 | 16,513 | 86–64 | W3 |
| 151 | September 23 | 7:00 p.m. CDT | @ Padres | L 4–9 | Curtis (9–8) | Niemann (0–1) | – | 3:00 | 4,788 | 86–65 | L1 |
| 152 | September 24 | 6:35 p.m. CDT | @ Braves | L 2–4 | Alexander (14–9) | Andújar (3–7) | Camp (20) | 2:39 | 24,897 | 86–66 | L2 |
| 153 | September 25 | 6:35 p.m. CDT | @ Braves | W 4–2 | Ryan (10–9) | Niekro (15–16) | Smith (8) | 2:39 | 7,926 | 87–66 | W1 |
| 154 | September 26 | 7:35 p.m. CDT | Reds | W 2–0 | Ruhle (11–4) | Seaver (10–8) | – | 2:02 | 42,486 | 88–66 | W2 |
| 155 | September 27 | 2:05 p.m. CDT | Reds | W 2–0 | Niekro (18–12) | Soto (10–7) | Smith (9) | 2:25 | 40,305 | 89–66 | W3 |
| 156 | September 28 | 2:05 p.m. CDT | Reds | L 5–8 | LaCoss (10–12) | Andújar (3–8) | Hume (24) | 2:52 | 32,756 | 89–67 | L1 |
| 157 | September 30 | 7:35 p.m. CDT | Braves | W 7–3 | Ryan (11–9) | Alexander (14–10) | Smith (10) | 2:41 | 31,973 | 90–67 | W1 |
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October: 3–3 (Home: 2–0; Away: 1–3)
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