| 2021 game log: 52–110 (Home: 27–54; Away: 25–56) |
April: 12–14 (Home: 4–10; Away: 8–4)
| # | Date | Opponent | Score | Win | Loss | Save | Attendance | Record | Streak/ Box |
| — | April 1 | @ Red Sox | Postponed (rain). Makeup date April 2.[5] |
| 1 | April 2 | @ Red Sox | 3–0 | Means (1–0) | Eovaldi (0–1) | Valdez (1) | 4,452 | 1–0 | W1 |
| 2 | April 3 | @ Red Sox | 4–2 | Plutko (1–0) | Houck (0–1) | Valdez (2) | 4,571 | 2–0 | W2 |
| 3 | April 4 | @ Red Sox | 11–3 | Zimmermann (1–0) | Richards (0–1) | — | 4,458 | 3–0 | W3 |
| 4 | April 5 | @ Yankees | 0–7 | Montgomery (1–0) | López (0–1) | — | 9,008 | 3–1 | L1 |
| 5 | April 6 | @ Yankees | 2–7 | Cole (1–0) | Kremer (0–1) | — | 9,404 | 3–2 | L2 |
| 6 | April 7 | @ Yankees | 4–3 (11) | Valdez (1–0) | Green (0–1) | Fry (1) | 10,254 | 4–2 | W1 |
| 7 | April 8 | Red Sox | 3–7 | Rodríguez (1–0) | Harvey (0–1) | — | 10,150 | 4–3 | L1 |
| 8 | April 10 | Red Sox | 4–6 (10) | Barnes (1–0) | Tate (0–1) | Andriese (1) | 9,307 | 4–4 | L2 |
| 9 | April 11 | Red Sox | 9–14 | Pivetta (2–0) | López (0–2) | — | 8,171 | 4–5 | L3 |
| — | April 12 | Mariners | Postponed (rain). Makeup date April 13 as part of doubleheader.[6] |
| 10 | April 13 | Mariners | 3–4 (8) | Montero (1–0) | Scott (0–1) | Graveman (1) | 4,147[a] | 4–6 | L4 |
| 11 | April 13 | Mariners | 7–6 (7) | Valdez (2–0) | Sadler (0–1) | — | 4,147[a] | 5–6 | W1 |
| — | April 14 | Mariners | Postponed (rain). Makeup date April 15 as part of doubleheader.[7] |
| 12 | April 15 | Mariners | 2–4 (7) | Gonzales (1–1) | Scott (0–2) | Graveman (2) | 5,060[b] | 5–7 | L1 |
| 13 | April 15 | Mariners | 1–2 (7) | Dunn (1–0) | Zimmermann (1–1) | Middleton (2) | 5,060[b] | 5–8 | L2 |
| 14 | April 16 | @ Rangers | 5–2 | López (1–2) | Foltynewicz (0–3) | Valdez (3) | 22,173 | 6–8 | W1 |
| 15 | April 17 | @ Rangers | 6–1 | Lakins (1–0) | Rodríguez (0–1) | — | 29,338 | 7–8 | W2 |
| 16 | April 18 | @ Rangers | 0–1 (10) | King (1–0) | Lakins (1–1) | — | 24,267 | 7–9 | L1 |
| 17 | April 20 | @ Marlins | 7–5 | Harvey (1–1) | Neidert (0–1) | Valdez (4) | 4,540 | 8–9 | W1 |
| 18 | April 21 | @ Marlins | 0–3 | Rogers (1–2) | Zimmermann (1–2) | García (4) | 4,028 | 8–10 | L1 |
| 19 | April 23 | Athletics | 1–3 | Irvin (2–2) | López (1–3) | Diekman (2) | 7,574 | 8–11 | L2 |
| 20 | April 24 | Athletics | 2–7 | Bassitt (2–2) | LeBlanc (0–1) | — | 7,616 | 8–12 | L3 |
| 21 | April 25 | Athletics | 8–1 | Means (2–0) | Luzardo (1–2) | — | 8,107 | 9–12 | W1 |
| 22 | April 26 | Yankees | 4–2 | Harvey (2–1) | García (0–1) | Valdez (5) | 6,367 | 10–12 | W2 |
| 23 | April 27 | Yankees | 1–5 | Kluber (1–2) | Zimmermann (1–3) | — | 6,662 | 10–13 | L1 |
| 24 | April 28 | Yankees | 0–7 | Germán (2–2) | Kremer (0–2) | — | 7,338 | 10–14 | L2 |
| 25 | April 29 | Yankees | 4–3 (10) | Scott (1–2) | Loaisiga (2–1) | — | 7,738 | 11–14 | W1 |
| 26 | April 30 | @ Athletics | 3–2 | Means (3–0) | Fiers (0–1) | Valdez (6) | 5,777 | 12–14 | W2 |
|
May: 5–23 (Home: 2–9; Away: 3–14)
| # | Date | Opponent | Score | Win | Loss | Save | Attendance | Record | Streak/Box |
| 27 | May 1 | @ Athletics | 8–4 | Harvey (3–1) | Luzardo (1–3) | — | 6,469 | 13–14 | W3 |
| 28 | May 2 | @ Athletics | 5–7 | Petit (4–0) | Lakins (1–2) | Trivino (5) | 5,862 | 13–15 | L1 |
| 29 | May 3 | @ Mariners | 5–3 | Sulser (1–0) | Misiewicz (2–1) | Valdez (7) | 5,776 | 14–15 | W1 |
| 30 | May 4 | @ Mariners | 2–5 | Montero (3–1) | Lakins (1–3) | — | 6,504 | 14–16 | L1 |
| 31 | May 5 | @ Mariners | 6–0 | Means (4–0) | Kikuchi (1–2) | — | 6,742 | 15–16 | W1 |
| 32 | May 7 | Red Sox | 2–6 | Rodríguez (5–0) | Harvey (3–2) | — | 7,724 | 15–17 | L1 |
| 33 | May 8 | Red Sox | 6–11 | Richards (2–2) | Lowther (0–1) | — | 10,598 | 15–18 | L2 |
| 34 | May 9 | Red Sox | 3–4 | Pivetta (5–0) | Kremer (0–3) | Barnes (8) | 10,274 | 15–19 | L3 |
| 35 | May 10 | Red Sox | 4–1 | Scott (2–2) | Andriese (1–2) | Valdez (8) | 6,826 | 16–19 | W1 |
| 36 | May 11 | @ Mets | 2–3 | Familia (1–0) | Valdez (2–1) | — | 7,930 | 16–20 | L1 |
| 37 | May 12 | @ Mets | 1–7 | Walker (3–1) | Harvey (3–3) | — | 8,035 | 16–21 | L2 |
| 38 | May 14 | Yankees | 4–5 | Kluber (3–2) | Lakins (1–4) | Loáisiga (2) | 10,809 | 16–22 | L3 |
| 39 | May 15 | Yankees | 2–8 | Germán (3–2) | López (1–4) | — | 10,767 | 16–23 | L4 |
| 40 | May 16 | Yankees | 10–6 | Zimmermann (2–3) | King (0–1) | — | 11,070 | 17–23 | W1 |
| 41 | May 18 | Rays | 6–13 | Kittredge (4–0) | Harvey (3–4) | — | 5,429 | 17–24 | L1 |
| 42 | May 19 | Rays | 7–9 | Thompson (3–2) | Fry (0–1) | Fairbanks (1) | 6,581 | 17–25 | L2 |
| 43 | May 20 | Rays | 1–10 | Hill (3–1) | Kremer (0–4) | — | 6,916 | 17–26 | L3 |
| 44 | May 21 | @ Nationals | 2–4 | Strasburg (1–1) | López (1–5) | — | 14,369 | 17–27 | L4 |
| 45 | May 22 | @ Nationals | 9–12 | Hudson (3–0) | Plutko (1–1) | Hand (6) | 15,440 | 17–28 | L5 |
| 46 | May 23 | @ Nationals | 5–6 | Corbin (3–3) | Harvey (3–5) | Hand (7) | 14,618 | 17–29 | L6 |
| 47 | May 24 | @ Twins | 3–8 | Alcalá (1–1) | Scott (2–3) | — | 8,530 | 17–30 | L7 |
| 48 | May 25 | @ Twins | 4–7 | Berríos (5–2) | Kremer (0–5) | Rogers (3) | 9,969 | 17–31 | L8 |
| 49 | May 26 | @ Twins | 2–3 | Pineda (3–2) | López (1–6) | Robles (3) | 10,574 | 17–32 | L9 |
| 50 | May 27 | @ White Sox | 1–5 | Cease (3–1) | Tate (0–2) | — | 9,671 | 17–33 | L10 |
| — | May 28 | @ White Sox | Postponed (rain). Makeup date May 29 as part of doubleheader. |
| 51 | May 29 | @ White Sox | 4–7 (7) | Keuchel (4–1) | Harvey (3–6) | Hendriks (11) | 20,029[c] | 17–34 | L11 |
| 52 | May 29 | @ White Sox | 1–3 (7) | Lynn (6–1) | Means (4–1) | Hendriks (12) | 20,029[c] | 17–35 | L12 |
| 53 | May 30 | @ White Sox | 1–3 | Giolito (5–4) | Tate (0–3) | Hendriks (13) | 21,067 | 17–36 | L13 |
| 54 | May 31 | Twins | 2–3 (10) | Rogers (3–3) | Plutko (1–2) | Robles (4) | 11,010 | 17–37 | L14 |
|
June: 10–17 (Home: 6–7; Away: 4–10)
| # | Date | Opponent | Score | Win | Loss | Save | Attendance | Record | Streak/Box |
| 55 | June 1 | Twins | 7–4 | Zimmermann (3–3) | Pineda (3–3) | Sulser (1) | 5,337 | 18–37 | W1 |
| 56 | June 2 | Twins | 6–3 | T. Wells (1–0) | Dobnak (1–5) | — | 5,945 | 19–37 | W2 |
| 57 | June 4 | Indians | 3–1 | Sulser (2–0) | Shaw (1–1) | Fry (2) | 12,009 | 20–37 | W3 |
| 58 | June 5 | Indians | 4–10 | Civale (8–2) | Means (4–2) | — | 9,969 | 20–38 | L1 |
| 59 | June 6 | Indians | 18–5 | López (2–6) | Quantrill (0–2) | — | 9,423 | 21–38 | W1 |
| 60 | June 8 | Mets | 10–3 | Zimmermann (4–3) | Peterson (1–5) | — | 9,431 | 22–38 | W2 |
| 61 | June 9 | Mets | 1–14 | Walker (5–2) | Harvey (3–7) | — | 9,584 | 22–39 | L1 |
| 62 | June 11 | @ Rays | 2–4 | Yarbrough (4–3) | Akin (0–1) | Fairbanks (2) | 6,211 | 22–40 | L2 |
| 63 | June 12 | @ Rays | 4–5 | McHugh (1–1) | López (2–7) | Castillo (11) | 9,225 | 22–41 | L3 |
| 64 | June 13 | @ Rays | 1–7 | Fleming (6–4) | Zimmermann (4–4) | — | 9,101 | 22–42 | L4 |
| 65 | June 14 | @ Indians | 3–4 | Sandlin (1–0) | Kremer (0–6) | Clase (10) | 11,181 | 22–43 | L5 |
| 66 | June 15 | @ Indians | 2–7 | Karinchak (4–2) | Harvey (3–8) | — | 12,025 | 22–44 | L6 |
| 67 | June 16 | @ Indians | 7–8 | Civale (10–2) | Akin (0–2) | Clase (11) | 12,825 | 22–45 | L7 |
| 68 | June 17 | @ Indians | 3–10 | Stephan (1–0) | López (2–8) | — | 15,121 | 22–46 | L8 |
| 67 | June 18 | Blue Jays | 7–1 | T. Wells (2–0) | Ray (4–3) | — | 13,284 | 23–46 | W1 |
| 70 | June 19 | Blue Jays | 7–10 | Romano (4–1) | Fry (0–2) | — | 10,721 | 23–47 | L1 |
| 71 | June 20 | Blue Jays | 4–7 | Ryu (6–4) | Harvey (3–9) | Chatwood (1) | 14,917 | 23–48 | L2 |
| 72 | June 21 | Astros | 2–10 | Odorizzi (2–3) | Akin (0–3) | — | 7,414 | 23–49 | L3 |
| 73 | June 22 | Astros | 1–3 | Greinke (8–2) | López (2–9) | Pressly (11) | 8,510 | 23–50 | L4 |
| 74 | June 23 | Astros | 0–13 | Urquidy (6–3) | Eshelman (0–1) | — | 10,013 | 23–51 | L5 |
| 75 | June 24 | @ Blue Jays | 0–9 | Kay (1–2) | Kremer (0–7) | — | 6,264 | 23–52 | L6 |
| 76 | June 25 | @ Blue Jays | 6–5 (10) | Fry (1–2) | Thornton (1–3) | Sulser (2) | 7,844 | 24–52 | W1 |
| 77 | June 26 | @ Blue Jays | 4–12 | Ryu (7–4) | Akin (0–4) | — | 5,913 | 24–53 | L1 |
| 78 | June 27 | @ Blue Jays | 2–5 | Stripling (3–4) | López (2–10) | Romano (6) | 6,044 | 24–54 | L2 |
| 79 | June 28 | @ Astros | 9–7 | Fry (2–2) | Bielak (2–3) | Plutko (1) | 24,419 | 25–54 | W1 |
| 80 | June 29 | @ Astros | 13–3 | A. Wells (1–0) | Garza (0–2) | Tate (1) | 30,346 | 26–54 | W2 |
| 81 | June 30 | @ Astros | 5–2 | Scott (3–3) | García (6–5) | Sulser (3) | 28,124 | 27–54 | W3 |
|
July: 10–12 (Home: 5–4; Away: 5–7)
| # | Date | Opponent | Score | Win | Loss | Save | Attendance | Record | Streak/Box |
| 82 | July 2 | @ Angels | 7–8 | Iglesias (5–3) | Fry (2–3) | — | 23,561 | 27–55 | L1 |
| 83 | July 3 | @ Angels | 1–4 | Cobb (6–3) | López (2–11) | Iglesias (16) | 28,160 | 27–56 | L2 |
| 84 | July 4 | @ Angels | 5–6 | Iglesias (6–3) | Sulser (2–1) | — | 18,955 | 27–57 | L3 |
| 85 | July 6 | Blue Jays | 7–5 | Watkins (1–0) | Matz (7–4) | — | 7,388 | 28–57 | W1 |
| 86 | July 7 | Blue Jays | 2–10 | Ryu (8–5) | Harvey (3–10) | — | 7,457 | 28–58 | L1 |
| — | July 8 | Blue Jays | Postponed (rain). Makeup date September 11 as part of doubleheader. |
| 87 | July 9 | White Sox | 1–12 | Keuchel (7–3) | López (2–12) | — | 12,077 | 28–59 | L2 |
| 88 | July 10 | White Sox | 3–8 | Giolito (7–6) | Eshelman (0–2) | Hendriks (23) | 26,391 | 28–60 | L3 |
| 89 | July 11 | White Sox | 5–7 (10) | Hendriks (4–2) | T. Wells (2–1) | Foster (1) | 11,600 | 28–61 | L4 |
| ASG | July 13 | @ Coors Field | AL vs. NL | Ohtani (1–0) | Burnes (0–1) | Hendriks (1) | 49,184 | — | N/A |
| 90 | July 16 | @ Royals | 2–9 | Staumont (1–2) | Akin (0–5) | — | 23,763 | 28–62 | L5 |
| 91 | July 17 | @ Royals | 8–4 | Fry (3–3) | Singer (3–7) | — | 27,292 | 29–62 | W1 |
| 92 | July 18 | @ Royals | 5–0 | Harvey (4–10) | Hernández (1–1) | — | 13,706 | 30–62 | W2 |
| 93 | July 19 | @ Rays | 6–1 | Watkins (2–0) | Yarbrough (6–4) | — | 9,922 | 31–62 | W3 |
| 94 | July 20 | @ Rays | 3–9 | McClanahan (4–3) | Means (4–3) | — | 10,399 | 31–63 | L1 |
| 95 | July 21 | @ Rays | 4–5 | McHugh (3–1) | Scott (3–4) | — | 8,968 | 31–64 | L2 |
| 96 | July 23 | Nationals | 6–1 | Fry (4–3) | Corbin (6–9) | — | 17,022 | 32–64 | W1 |
| 97 | July 24 | Nationals | 5–3 | Harvey (5–10) | Lester (3–5) | Tate (2) | 30,898 | 33–64 | W2 |
| 98 | July 25 | Nationals | 5–4 | Sulser (3–1) | Hand (5–4) | — | 15,690 | 34–64 | W3 |
| 99 | July 27 | Marlins | 3–7 | Alcántara (6–9) | Watkins (2–1) | — | 10,098 | 34–65 | L1 |
| 100 | July 28 | Marlins | 8–7 | Scott (4–4) | Okert (0–1) | — | 8,363 | 35–65 | W1 |
| 101 | July 29 | @ Tigers | 2–6 | Mize (6–5) | A. Wells (1–1) | — | 15,833 | 35–66 | L1 |
| 102 | July 30 | @ Tigers | 4–3 | Harvey (6–10) | Skubal (6–10) | Sulser (4) | 18,861 | 36–66 | W1 |
| 103 | July 31 | @ Tigers | 5–2 | Means (5–3) | Manning (2–4) | Sulser (5) | 25,132 | 37–66 | W2 |
|
August: 4–24 (Home: 2–13; Away: 2–11)
| # | Date | Opponent | Score | Win | Loss | Save | Attendance | Record | Streak/Box |
| 104 | August 1 | @ Tigers | 2–6 | Ramírez (1–0) | Watkins (2–2) | — | 17,134 | 37–67 | L1 |
| 105 | August 2 | @ Yankees | 7–1 | López (3–12) | Heaney (6–8) | — | 28,879 | 38–67 | W1 |
| 106 | August 3 | @ Yankees | 1–13 | Gil (1–0) | Wells (1–2) | — | 30,815 | 38–68 | L1 |
| 107 | August 4 | @ Yankees | 3–10 | Loáisiga (8–4) | Sulser (3–2) | — | 30,055 | 38–69 | L2 |
| 108 | August 6 | Rays | 6–10 | Rasmussen (1–1) | Fry (4–4) | — | 11,320 | 38–70 | L3 |
| 109 | August 7 | Rays | 3–12 | McClanahan (6–4) | Watkins (2–3) | — | 18,545 | 38–71 | L4 |
| 110 | August 8 | Rays | 6–9 | Chargois (2–0) | Fry (4–5) | — | 10,576 | 38–72 | L5 |
| 111 | August 10 | Tigers | 4–9 | Funkhouser (6–1) | Akin (0–6) | — | 7,124 | 38–73 | L6 |
| 112 | August 11 | Tigers | 2–5 | Skubal (8–10) | Harvey (6–11) | Soto (14) | 8,990 | 38–74 | L7 |
| 113 | August 12 | Tigers | 4–6 | Manning (3–5) | Means (5–4) | Fulmer (7) | 8,382 | 38–75 | L8 |
| 114 | August 13 | @ Red Sox | 1–8 | Pivetta (9–5) | Watkins (2–4) | Richards (1) | 28,022 | 38–76 | L9 |
| 115 | August 14 | @ Red Sox | 2–16 | Sale (1–0) | López (3–13) | — | 33,118 | 38–77 | L10 |
| 116 | August 15 | @ Red Sox | 2–6 | Rodríguez (9–6) | Akin (0–7) | — | 28,935 | 38–78 | L11 |
| 117 | August 16 | @ Rays | 2–9 | Fleming (10–6) | Harvey (6–12) | — | 5,460 | 38–79 | L12 |
| 118 | August 17 | @ Rays | 0–10 | Ellis (1–0) | Means (5–5) | — | 4,795 | 38–80 | L13 |
| 119 | August 18 | @ Rays | 4–8 | Yarbrough (7–4) | Watkins (2–5) | — | 6,673 | 38–81 | L14 |
| 120 | August 19 | @ Rays | 2–7 | McClanahan (8–4) | López (3–14) | — | 5,826 | 38–82 | L15 |
| 121 | August 20 | Braves | 0–3 | Fried (11–7) | Akin (0–8) | — | 13,583 | 38–83 | L16 |
| 122 | August 21 | Braves | 4–5 | Smyly (9–3) | Harvey (6–13) | Smith (27) | 15,774 | 38–84 | L17 |
| 123 | August 22 | Braves | 1–3 | Toussaint (3–2) | Means (5–6) | Smith (28) | 11,180 | 38–85 | L18 |
| 124 | August 24 | Angels | 8–14 | Guerra (4–2) | Watkins (2–6) | — | 8,781 | 38–86 | L19 |
| 125 | August 25 | Angels | 10–6 | Scott (5–4) | Petricka (0–1) | — | 15,867 | 39–86 | W1 |
| 126 | August 26 | Angels | 13–1 | Akin (1–8) | Peguero (0–1) | — | 10,211 | 40–86 | W2 |
| 127 | August 27 | Rays | 3–6 | McClanahan (9–4) | Harvey (6–14) | Mazza (1) | 7,155 | 40–87 | L1 |
| 128 | August 28 | Rays | 3–4 | Chargois (4–0) | Sulser (3–3) | Kittredge (4) | 11,110 | 40–88 | L2 |
| 129 | August 29 | Rays | 8–12 | Chargois (5–0) | Watkins (2–7) | — | 8,353 | 40–89 | L3 |
| 130 | August 30 | @ Blue Jays | 3–7 | Ray (10–5) | Tate (0–4) | Romano (14) | 14,406 | 40–90 | L4 |
| 131 | August 31 | @ Blue Jays | 4–2 | Akin (2–8) | Ryu (12–8) | Sulser (6) | 13,963 | 41–90 | W1 |
|
September/October: 11–20 (Home: 8–10; Away: 3–10)
| # | Date | Opponent | Score | Win | Loss | Save | Attendance | Record | Streak/Box |
| 132 | September 1 | @ Blue Jays | 4–5 | Mayza (5–2) | Tate (0–5) | Romano (15) | 14,262 | 41–91 | L1 |
| 133 | September 3 | @ Yankees | 3–4 (10) | Holmes (6–2) | Tate (0–6) | — | 34,085 | 41–92 | L2 |
| 134 | September 4 | @ Yankees | 4–3 | Sulser (4–3) | Chapman (5–4) | — | 34,571 | 42–92 | W1 |
| 135 | September 5 | @ Yankees | 8–7 | Diplán (1–0) | Heaney (8–9) | T. Wells (1) | 33,091 | 43–92 | W2 |
| 136 | September 6 | Royals | 2–3 | Tapia (2–0) | Sulser (4–4) | Barlow (11) | 11,973 | 43–93 | L1 |
| 137 | September 7 | Royals | 7–3 | Baumann (1–0) | Kowar (0–3) | — | 4,981 | 44–93 | W1 |
| 138 | September 8 | Royals | 9–8 | Barreda (1–0) | Staumont (3–3) | T. Wells (2) | 4,965 | 45–93 | W2 |
| 139 | September 9 | Royals | 0–6 | Hernández (6–1) | Means (5–7) | — | 5,087 | 45–94 | L1 |
| 140 | September 10 | Blue Jays | 6–3 | Greene (1–0) | Merryweather (0–1) | Sulser (7) | 11,851 | 46–94 | W1 |
| 141 | September 11 (1) | Blue Jays | 10–11 | Pearson (1–1) | T. Wells (2–2) | Romano (17) | N/A | 46–95 | L1 |
| 142 | September 11 (2) | Blue Jays | 2–11 | Richards (7–2) | Akin (2–9) | — | 10,219 | 46–96 | L2 |
| 143 | September 12 | Blue Jays | 7–22 | Matz (12–7) | Lowther (0–2) | — | 8,474 | 46–97 | L3 |
| 144 | September 14 | Yankees | 2–7 | Cole (15–7) | A. Wells (1–3) | — | 10,235 | 46–98 | L4 |
| 145 | September 15 | Yankees | 3–4 | Peralta (5–3) | T. Wells (2–3) | Chapman (27) | 10,402 | 46–99 | L5 |
| 146 | September 16 | Yankees | 3–2 (10) | Sulser (5–4) | Peralta (5–4) | — | 20,164 | 47–99 | W1 |
| 147 | September 17 | @ Red Sox | 1–7 | Sale (4–0) | Akin (2–10) | — | 29,811 | 47–100 | L1 |
| 148 | September 18 | @ Red Sox | 3–9 | Houck (1–4) | Baumann (1–1) | — | 30,027 | 47–101 | L2 |
| 149 | September 19 | @ Red Sox | 6–8 | Sawamura (5–1) | Greene (1–1) | Richards (3) | 27,010 | 47–102 | L3 |
| 150 | September 20 | @ Phillies | 2–0 | Means (6–7) | Suárez (6–5) | T. Wells (3) | 21,440 | 48–102 | W1 |
| 151 | September 21 | @ Phillies | 2–3 (10) | Kennedy (3–1) | Valdez (2–2) | — | 18,955 | 48–103 | L1 |
| 152 | September 22 | @ Phillies | 3–4 | Alvarado (7–1) | Greene (1–2) | Kennedy (25) | 18,133 | 48–104 | L2 |
| 153 | September 23 | Rangers | 3–0 | Lowther (1–2) | Otto (0–3) | T. Wells (4) | 6,328 | 49–104 | W1 |
| 154 | September 24 | Rangers | 5–8 | Sborz (4–3) | Greene (1–3) | Barlow (8) | 7,935 | 49–105 | L1 |
| 155 | September 25 | Rangers | 3–2 | Kriske (2–1) | Lyles (9–13) | Tate (3) | 10,645 | 50–105 | W1 |
| 156 | September 26 | Rangers | 4–7 | Cotton (2–0) | Means (6–8) | Barlow (9) | 13,495 | 50–106 | L1 |
| 157 | September 28 | Red Sox | 4–2 | Diplán (2–0) | Sale (5–1) | Sulser (8) | 8,098 | 51–106 | W1 |
| 158 | September 29 | Red Sox | 0–6 | Eovaldi (11–9) | Lowther (1–3) | — | 8,732 | 51–107 | L1 |
| 159 | September 30 | Red Sox | 6–2 | A. Wells (2–3) | Pivetta (9–8) | — | 13,012 | 52–107 | W1 |
| 160 | October 1 | @ Blue Jays | 4–6 | Matz (14–7) | Eshelman (0–3) | Romano (23) | 28,855 | 52–108 | L1 |
| 161 | October 2 | @ Blue Jays | 1–10 | Manoah (9–2) | Means (6–9) | — | 29,916 | 52–109 | L2 |
| 162 | October 3 | @ Blue Jays | 4–12 | Ryu (14–10) | Zimmermann (4–5) | — | 29,942 | 52–110 | L3 |
|