| 1 | Tue Apr 2 | at Blue Jays | W4-1 | 1-0 | 1.000 | Rogers Centre · Toronto, ON |
| 2 | Wed Apr 3 | at Blue Jays | W3-2 (11) | 2-0 | 1.000 | Rogers Centre · Toronto, ON |
| 3 | Thu Apr 4 | at Blue Jays | L8-10 | 2-1 | .667 | Rogers Centre · Toronto, ON |
| 4 | Fri Apr 5 | at Rays | L0-4 | 2-2 | .500 | Tropicana Field · St. Petersburg, FL |
| 5 | Sat Apr 6 | at Rays | L0-6 | 2-3 | .400 | Tropicana Field · St. Petersburg, FL |
| 6 | Sun Apr 7 | at Rays | W13-0 | 3-3 | .500 | Tropicana Field · St. Petersburg, FL |
| 7 | Mon Apr 8 | vs Yankees | L6-11 | 3-4 | .429 | Progressive Field · Cleveland, OH |
| 8 | Tue Apr 9 | vs Yankees | L1-14 | 3-5 | .375 | Progressive Field · Cleveland, OH |
| 9 | Fri Apr 12 | vs White Sox | W1-0 | 4-5 | .444 | Progressive Field · Cleveland, OH |
| 10 | Sat Apr 13 | vs White Sox | W9-4 | 5-5 | .500 | Progressive Field · Cleveland, OH |
| 11 | Sun Apr 14 | vs White Sox | L1-3 | 5-6 | .455 | Progressive Field · Cleveland, OH |
| 12 | Tue Apr 16 | vs Red Sox | L2-7 | 5-7 | .417 | Progressive Field · Cleveland, OH |
| 13 | Wed Apr 17 | vs Red Sox | L3-6 | 5-8 | .385 | Progressive Field · Cleveland, OH |
| 14 | Thu Apr 18 | vs Red Sox | L3-6 | 5-9 | .357 | Progressive Field · Cleveland, OH |
| 15 | Fri Apr 19 | at Astros | L2-3 | 5-10 | .333 | Minute Maid Park · Houston, TX |
| 16 | Sat Apr 20 | at Astros | W19-6 | 6-10 | .375 | Minute Maid Park · Houston, TX |
| 17 | Sun Apr 21 | at Astros | W5-4 | 7-10 | .412 | Minute Maid Park · Houston, TX |
| 18 | Mon Apr 22 | at White Sox | W3-2 | 8-10 | .444 | Guaranteed Rate Field · Chicago, IL |
| 19 | Wed Apr 24 | at White Sox | L2-3 | 8-11 | .421 | Guaranteed Rate Field · Chicago, IL |
| 20 | Sat Apr 27 | at Royals | L2-3 | 8-12 | .400 | Kauffman Stadium · Kansas City, MO |
| 21 | Sun Apr 28 | at Royals | L0-9 | 8-13 | .381 | Kauffman Stadium · Kansas City, MO |
| 22 | Sun Apr 28 | at Royals | W10-3 | 9-13 | .409 | Kauffman Stadium · Kansas City, MO |
| 23 | Mon Apr 29 | at Royals | W9-0 | 10-13 | .435 | Kauffman Stadium · Kansas City, MO |
| 24 | Tue Apr 30 | vs Phillies | W14-2 | 11-13 | .458 | Progressive Field · Cleveland, OH |
| 25 | Wed May 1 | vs Phillies | W6-0 | 12-13 | .480 | Progressive Field · Cleveland, OH |
| 26 | Fri May 3 | vs Twins | W7-6 (10) | 13-13 | .500 | Progressive Field · Cleveland, OH |
| 27 | Sat May 4 | vs Twins | W7-3 | 14-13 | .519 | Progressive Field · Cleveland, OH |
| 28 | Sun May 5 | vs Twins | L2-4 | 14-14 | .500 | Progressive Field · Cleveland, OH |
| 29 | Mon May 6 | vs Athletics | W7-3 | 15-14 | .517 | Progressive Field · Cleveland, OH |
| 30 | Tue May 7 | vs Athletics | W1-0 | 16-14 | .533 | Progressive Field · Cleveland, OH |
| 31 | Wed May 8 | vs Athletics | W4-3 | 17-14 | .548 | Progressive Field · Cleveland, OH |
| 32 | Thu May 9 | vs Athletics | W9-2 | 18-14 | .563 | Progressive Field · Cleveland, OH |
| 33 | Fri May 10 | at Tigers | L4-10 | 18-15 | .545 | Comerica Park · Detroit, MI |
| 34 | Sat May 11 | at Tigers | W7-6 | 19-15 | .559 | Comerica Park · Detroit, MI |
| 35 | Sun May 12 | at Tigers | W4-3 (10) | 20-15 | .571 | Comerica Park · Detroit, MI |
| 36 | Mon May 13 | vs Yankees | W1-0 | 21-15 | .583 | Progressive Field · Cleveland, OH |
| 37 | Mon May 13 | vs Yankees | L0-7 | 21-16 | .568 | Progressive Field · Cleveland, OH |
| 38 | Tue May 14 | at Phillies | L2-6 | 21-17 | .553 | Citizens Bank Park · Philadelphi, PA |
| 39 | Wed May 15 | at Phillies | W10-4 | 22-17 | .564 | Citizens Bank Park · Philadelphi, PA |
| 40 | Fri May 17 | vs Mariners | W6-3 (10) | 23-17 | .575 | Progressive Field · Cleveland, OH |
| 41 | Sat May 18 | vs Mariners | W5-4 | 24-17 | .585 | Progressive Field · Cleveland, OH |
| 42 | Sun May 19 | vs Mariners | W6-0 | 25-17 | .595 | Progressive Field · Cleveland, OH |
| 43 | Mon May 20 | vs Mariners | W10-8 (10) | 26-17 | .605 | Progressive Field · Cleveland, OH |
| 44 | Tue May 21 | vs Tigers | L1-5 | 26-18 | .591 | Progressive Field · Cleveland, OH |
| 45 | Wed May 22 | vs Tigers | L7-11 | 26-19 | .578 | Progressive Field · Cleveland, OH |
| 46 | Thu May 23 | at Red Sox | W12-3 | 27-19 | .587 | Fenway Park · Boston, MA |
| 47 | Fri May 24 | at Red Sox | L1-8 | 27-20 | .574 | Fenway Park · Boston, MA |
| 48 | Sat May 25 | at Red Sox | L4-7 | 27-21 | .563 | Fenway Park · Boston, MA |
| 49 | Sun May 26 | at Red Sox | L5-6 | 27-22 | .551 | Fenway Park · Boston, MA |
| 50 | Mon May 27 | at Reds | L2-4 | 27-23 | .540 | Great American Ball Park · Cincinnati, OH |
| 51 | Tue May 28 | at Reds | L2-8 | 27-24 | .529 | Great American Ball Park · Cincinnati, OH |
| 52 | Wed May 29 | vs Reds | W5-2 | 28-24 | .538 | Progressive Field · Cleveland, OH |
| 53 | Thu May 30 | vs Reds | W7-1 | 29-24 | .547 | Progressive Field · Cleveland, OH |
| 54 | Fri May 31 | vs Rays | L2-9 | 29-25 | .537 | Progressive Field · Cleveland, OH |
| 55 | Sat Jun 1 | vs Rays | W5-0 | 30-25 | .545 | Progressive Field · Cleveland, OH |
| 56 | Sun Jun 2 | vs Rays | L3-11 | 30-26 | .536 | Progressive Field · Cleveland, OH |
| 57 | Mon Jun 3 | at Yankees | L4-7 | 30-27 | .526 | Yankee Stadium · The Bronx, NY |
| 58 | Tue Jun 4 | at Yankees | L3-4 | 30-28 | .517 | Yankee Stadium · The Bronx, NY |
| 59 | Wed Jun 5 | at Yankees | L4-6 | 30-29 | .508 | Yankee Stadium · The Bronx, NY |
| 60 | Fri Jun 7 | at Tigers | L5-7 | 30-30 | .500 | Comerica Park · Detroit, MI |
| 61 | Sat Jun 8 | at Tigers | L4-6 | 30-31 | .492 | Comerica Park · Detroit, MI |
| 62 | Sun Jun 9 | at Tigers | L1-4 | 30-32 | .484 | Comerica Park · Detroit, MI |
| 63 | Mon Jun 10 | at Rangers | L3-6 | 30-33 | .476 | Globe Life Field · Arlington, TX |
| 64 | Tue Jun 11 | at Rangers | W5-2 | 31-33 | .484 | Globe Life Field · Arlington, TX |
| 65 | Wed Jun 12 | at Rangers | W5-2 | 32-33 | .492 | Globe Life Field · Arlington, TX |
| 66 | Fri Jun 14 | vs Nationals | W2-1 | 33-33 | .500 | Progressive Field · Cleveland, OH |
| 67 | Sat Jun 15 | vs Nationals | L6-7 | 33-34 | .493 | Progressive Field · Cleveland, OH |
| 68 | Sun Jun 16 | vs Nationals | W2-0 | 34-34 | .500 | Progressive Field · Cleveland, OH |
| 69 | Mon Jun 17 | vs Royals | L1-2 | 34-35 | .493 | Progressive Field · Cleveland, OH |
| 70 | Tue Jun 18 | vs Royals | W4-3 | 35-35 | .500 | Progressive Field · Cleveland, OH |
| 71 | Wed Jun 19 | vs Royals | W6-3 | 36-35 | .507 | Progressive Field · Cleveland, OH |
| 72 | Fri Jun 21 | vs Twins | W5-1 | 37-35 | .514 | Progressive Field · Cleveland, OH |
| 73 | Sat Jun 22 | vs Twins | W8-7 | 38-35 | .521 | Progressive Field · Cleveland, OH |
| 74 | Sun Jun 23 | vs Twins | L3-5 | 38-36 | .514 | Progressive Field · Cleveland, OH |
| 75 | Mon Jun 24 | at Orioles | W5-2 | 39-36 | .520 | Camden Yards · Baltimore, MD |
| 76 | Tue Jun 25 | at Orioles | L3-6 | 39-37 | .513 | Camden Yards · Baltimore, MD |
| 77 | Wed Jun 26 | at Orioles | W4-3 | 40-37 | .519 | Camden Yards · Baltimore, MD |
| 78 | Thu Jun 27 | at Orioles | L3-7 | 40-38 | .513 | Camden Yards · Baltimore, MD |
| 79 | Fri Jun 28 | at White Sox | W19-10 | 41-38 | .519 | Guaranteed Rate Field · Chicago, IL |
| 80 | Fri Jun 28 | at White Sox | W9-8 | 42-38 | .525 | Guaranteed Rate Field · Chicago, IL |
| 81 | Sat Jun 29 | at White Sox | W4-3 | 43-38 | .531 | Guaranteed Rate Field · Chicago, IL |
| 82 | Sun Jun 30 | at White Sox | W4-0 | 44-38 | .537 | Guaranteed Rate Field · Chicago, IL |
| 83 | Tue Jul 2 | at Royals | W6-5 | 45-38 | .542 | Kauffman Stadium · Kansas City, MO |
| 84 | Wed Jul 3 | at Royals | L5-6 | 45-39 | .536 | Kauffman Stadium · Kansas City, MO |
| 85 | Thu Jul 4 | at Royals | L7-10 | 45-40 | .529 | Kauffman Stadium · Kansas City, MO |
| 86 | Fri Jul 5 | vs Tigers | L0-7 | 45-41 | .523 | Progressive Field · Cleveland, OH |
| 87 | Sat Jul 6 | vs Tigers | L4-9 | 45-42 | .517 | Progressive Field · Cleveland, OH |
| 88 | Sun Jul 7 | vs Tigers | W9-6 | 46-42 | .523 | Progressive Field · Cleveland, OH |
| 89 | Mon Jul 8 | vs Tigers | L2-4 (10) | 46-43 | .517 | Progressive Field · Cleveland, OH |
| 90 | Tue Jul 9 | vs Blue Jays | W3-0 | 47-43 | .522 | Progressive Field · Cleveland, OH |
| 91 | Wed Jul 10 | vs Blue Jays | L4-5 | 47-44 | .516 | Progressive Field · Cleveland, OH |
| 92 | Thu Jul 11 | vs Blue Jays | W4-2 | 48-44 | .522 | Progressive Field · Cleveland, OH |
| 93 | Fri Jul 12 | vs Royals | W3-0 | 49-44 | .527 | Progressive Field · Cleveland, OH |
| 94 | Sat Jul 13 | vs Royals | W5-3 | 50-44 | .532 | Progressive Field · Cleveland, OH |
| 95 | Sun Jul 14 | vs Royals | W6-4 | 51-44 | .537 | Progressive Field · Cleveland, OH |
| 96 | Fri Jul 19 | at Twins | L2-3 | 51-45 | .531 | Target Field · Minneapolis, MN |
| 97 | Sat Jul 20 | at Twins | L2-3 | 51-46 | .526 | Target Field · Minneapolis, MN |
| 98 | Sun Jul 21 | at Twins | W7-1 | 52-46 | .531 | Target Field · Minneapolis, MN |
| 99 | Mon Jul 22 | at Mariners | L1-2 | 52-47 | .525 | T-Mobile Park · Seattle, WA |
| 100 | Tue Jul 23 | at Mariners | L3-4 | 52-48 | .520 | T-Mobile Park · Seattle, WA |
| 101 | Wed Jul 24 | at Mariners | W10-1 | 53-48 | .525 | T-Mobile Park · Seattle, WA |
| 102 | Fri Jul 26 | vs Rangers | W11-8 (11) | 54-48 | .529 | Progressive Field · Cleveland, OH |
| 103 | Sat Jul 27 | vs Rangers | W1-0 | 55-48 | .534 | Progressive Field · Cleveland, OH |
| 104 | Sun Jul 28 | vs Rangers | W6-0 | 56-48 | .538 | Progressive Field · Cleveland, OH |
| 105 | Mon Jul 29 | vs White Sox | W3-2 | 57-48 | .543 | Progressive Field · Cleveland, OH |
| 106 | Tue Jul 30 | vs White Sox | W7-4 | 58-48 | .547 | Progressive Field · Cleveland, OH |
| 107 | Wed Jul 31 | vs White Sox | W6-5 (10) | 59-48 | .551 | Progressive Field · Cleveland, OH |
| 108 | Thu Aug 1 | vs White Sox | W6-1 | 60-48 | .556 | Progressive Field · Cleveland, OH |
| 109 | Fri Aug 2 | at Marlins | L0-10 | 60-49 | .550 | LoanDepot Park · Miami, FL |
| 110 | Sat Aug 3 | at Marlins | W4-3 | 61-49 | .555 | LoanDepot Park · Miami, FL |
| 111 | Sun Aug 4 | at Marlins | W2-0 | 62-49 | .559 | LoanDepot Park · Miami, FL |
| 112 | Mon Aug 5 | vs Tigers | L2-4 | 62-50 | .554 | Progressive Field · Cleveland, OH |
| 113 | Tue Aug 6 | vs Tigers | L1-5 | 62-51 | .549 | Progressive Field · Cleveland, OH |
| 114 | Wed Aug 7 | vs Tigers | L5-6 (14) | 62-52 | .544 | Progressive Field · Cleveland, OH |
| 115 | Thu Aug 8 | vs Tigers | L3-10 | 62-53 | .539 | Progressive Field · Cleveland, OH |
| 116 | Fri Aug 9 | vs Angels | L2-5 | 62-54 | .534 | Progressive Field · Cleveland, OH |
| 117 | Sat Aug 10 | vs Angels | L2-7 | 62-55 | .530 | Progressive Field · Cleveland, OH |
| 118 | Sun Aug 11 | vs Angels | W6-5 | 63-55 | .534 | Progressive Field · Cleveland, OH |
| 119 | Mon Aug 12 | at Twins | L0-3 | 63-56 | .529 | Target Field · Minneapolis, MN |
| 120 | Tue Aug 13 | at Twins | W5-2 | 64-56 | .533 | Target Field · Minneapolis, MN |
| 121 | Wed Aug 14 | at Twins | W9-8 (12) | 65-56 | .537 | Target Field · Minneapolis, MN |
| 122 | Fri Aug 16 | at Athletics | L2-3 | 65-57 | .533 | RingCentral Coliseum · Oakland, CA |
| 123 | Sat Aug 17 | at Athletics | W7-1 | 66-57 | .537 | RingCentral Coliseum · Oakland, CA |
| 124 | Sun Aug 18 | at Athletics | L3-7 | 66-58 | .532 | RingCentral Coliseum · Oakland, CA |
| 125 | Mon Aug 19 | at Angels | W5-2 | 67-58 | .536 | Angel Stadium · Anaheim, CA |
| 126 | Tue Aug 20 | at Angels | W4-1 (14) | 68-58 | .540 | Angel Stadium · Anaheim, CA |
| 127 | Wed Aug 21 | at Angels | W3-1 | 69-58 | .543 | Angel Stadium · Anaheim, CA |
| 128 | Fri Aug 23 | vs Twins | L1-5 | 69-59 | .539 | Progressive Field · Cleveland, OH |
| 129 | Sat Aug 24 | vs Twins | W7-2 | 70-59 | .543 | Progressive Field · Cleveland, OH |
| 130 | Sun Aug 25 | vs Twins | W3-1 | 71-59 | .546 | Progressive Field · Cleveland, OH |
| 131 | Tue Aug 27 | at Braves | L0-2 | 71-60 | .542 | Truist Park · Cumberland, GA |
| 132 | Wed Aug 28 | at Braves | L2-3 | 71-61 | .538 | Truist Park · Cumberland, GA |
| 133 | Thu Aug 29 | at Braves | L1-3 | 71-62 | .534 | Truist Park · Cumberland, GA |
| 134 | Fri Aug 30 | at Tigers | L2-7 | 71-63 | .530 | Comerica Park · Detroit, MI |
| 135 | Sat Aug 31 | at Tigers | L5-10 | 71-64 | .526 | Comerica Park · Detroit, MI |
| 136 | Sun Sep 1 | at Tigers | W4-0 | 72-64 | .529 | Comerica Park · Detroit, MI |
| 137 | Mon Sep 2 | vs Orioles | L2-7 | 72-65 | .526 | Progressive Field · Cleveland, OH |
| 138 | Tue Sep 3 | vs Orioles | W4-3 | 73-65 | .529 | Progressive Field · Cleveland, OH |
| 139 | Wed Sep 4 | vs Orioles | W6-4 | 74-65 | .532 | Progressive Field · Cleveland, OH |
| 140 | Fri Sep 6 | vs Mets | W8-1 | 75-65 | .536 | Progressive Field · Cleveland, OH |
| 141 | Sat Sep 7 | vs Mets | W9-4 | 76-65 | .539 | Progressive Field · Cleveland, OH |
| 142 | Sun Sep 8 | vs Mets | L1-2 | 76-66 | .535 | Progressive Field · Cleveland, OH |
| 143 | Mon Sep 9 | vs Royals | W4-3 | 77-66 | .538 | Progressive Field · Cleveland, OH |
| 144 | Tue Sep 10 | vs Royals | L3-6 | 77-67 | .535 | Progressive Field · Cleveland, OH |
| 145 | Wed Sep 11 | vs Royals | L2-6 | 77-68 | .531 | Progressive Field · Cleveland, OH |
| 146 | Thu Sep 12 | at White Sox | W14-3 | 78-68 | .534 | Guaranteed Rate Field · Chicago, IL |
| 147 | Fri Sep 13 | at White Sox | W3-1 | 79-68 | .537 | Guaranteed Rate Field · Chicago, IL |
| 148 | Sat Sep 14 | at White Sox | W8-1 | 80-68 | .541 | Guaranteed Rate Field · Chicago, IL |
| 149 | Sun Sep 15 | at White Sox | W7-1 | 81-68 | .544 | Guaranteed Rate Field · Chicago, IL |
| 150 | Mon Sep 16 | at Royals | L1-7 | 81-69 | .540 | Kauffman Stadium · Kansas City, MO |
| 151 | Tue Sep 17 | at Royals | W5-3 | 82-69 | .543 | Kauffman Stadium · Kansas City, MO |
| 152 | Wed Sep 18 | at Royals | L2-7 | 82-70 | .539 | Kauffman Stadium · Kansas City, MO |
| 153 | Thu Sep 19 | vs Astros | W2-1 (11) | 83-70 | .542 | Progressive Field · Cleveland, OH |
| 154 | Fri Sep 20 | vs Astros | W2-1 | 84-70 | .545 | Progressive Field · Cleveland, OH |
| 155 | Sat Sep 21 | vs Astros | W4-1 | 85-70 | .548 | Progressive Field · Cleveland, OH |
| 156 | Sun Sep 22 | vs Astros | W9-2 | 86-70 | .551 | Progressive Field · Cleveland, OH |
| 157 | Tue Sep 24 | vs White Sox | W5-4 | 87-70 | .554 | Progressive Field · Cleveland, OH |
| 158 | Wed Sep 25 | vs White Sox | W7-2 | 88-70 | .557 | Progressive Field · Cleveland, OH |
| 159 | Thu Sep 26 | at Twins | W6-5 | 89-70 | .560 | Target Field · Minneapolis, MN |
| 160 | Fri Sep 27 | at Twins | W12-6 | 90-70 | .563 | Target Field · Minneapolis, MN |
| 161 | Sat Sep 28 | at Twins | W5-1 | 91-70 | .565 | Target Field · Minneapolis, MN |
| 162 | Sun Sep 29 | at Twins | W5-1 | 92-70 | .568 | Target Field · Minneapolis, MN |
| 163 | Wed Oct 2 | vs Rays | L0-4 | 0-1 | .000 | Progressive Field · Cleveland, OH |