| 2021-08-05 20:30:15August 5, 2021 | HAM  | 6 - 19 |  WPG | IG Field |
| 2021-08-06 21:30:53August 6, 2021 | BC  | 29 - 33 |  SSK | Mosaic Stadium |
| 2021-08-07 19:00:13August 7, 2021 | TOR  | 23 - 20 |  CGY | McMahon Stadium |
| 2021-08-07 22:00:15August 7, 2021 | OTT  | 16 - 12 |  EDM | Commonwealth Stadium |
| 2021-08-12 21:30:40August 12, 2021 | BC | 15 - 9 | CGY | McMahon Stadium |
| 2021-08-13 20:30:09August 13, 2021 | TOR | 7 - 20 | WPG | IG Field |
| 2021-08-14 19:00:35August 14, 2021 | MTL  | 30 - 13 | EDM | Commonwealth Stadium |
| 2021-08-14 21:00:50August 14, 2021 | HAM | 8 - 30 | SSK | Mosaic Stadium |
| 2021-08-19 22:00:00August 19, 2021 | EDM | 21 - 16 | BC | BC Place |
| 2021-08-20 21:30:00August 20, 2021 | MTL | 22 - 28 | CGY | McMahon Stadium |
| 2021-08-21 16:00:00August 21, 2021 | WPG | 23 - 30 | TOR | BMO Field |
| 2021-08-21 19:00:00August 21, 2021 | OTT | 10 - 23 | SSK | Mosaic Stadium |
| 2021-08-27 19:30:00August 27, 2021 | HAM | 27 - 10 | MTL | |
| 2021-08-28 19:00:00August 28, 2021 | BC | 24 - 12 | OTT | TD Place Stadium |
| 2021-08-29 19:00:00August 29, 2021 | CGY | 16 - 18 | WPG | IG Field |
| 2021-09-03 19:30:00September 3, 2021 | MTL | 51 - 29 | OTT | TD Place Stadium |
| 2021-09-05 18:00:00September 5, 2021 | WPG | 23 - 8 | SSK | Mosaic Stadium |
| 2021-09-06 13:00:00September 6, 2021 | TOR | 19 - 32 | HAM | Tim Hortons Field |
| 2021-09-06 16:30:00September 6, 2021 | EDM | 32 - 20 | CGY | McMahon Stadium |
| 2021-09-10 19:30:00September 10, 2021 | HAM | 16 - 17 | TOR | BMO Field |
| 2021-09-11 16:00:00September 11, 2021 | SSK | 9 - 33 | WPG | IG Field |
| 2021-09-11 19:00:00September 11, 2021 | CGY | 32 - 16 | EDM | Commonwealth Stadium |
| 2021-09-11 22:00:00September 11, 2021 | OTT | 13 - 45 | BC | BC Place |
| 2021-09-17 19:00:00September 17, 2021 | CGY | 17 - 23 | HAM | Tim Hortons Field |
| 2021-09-17 21:45:00September 17, 2021 | TOR | 16 - 30 | SSK | Mosaic Stadium |
| 2021-09-18 19:00:00September 18, 2021 | BC | 27 - 18 | MTL | |
| 2021-09-18 21:45:00September 18, 2021 | WPG | 37 - 22 | EDM | Commonwealth Stadium |
| 2021-09-22 19:30:00September 22, 2021 | HAM | 24 - 7 | OTT | TD Place Stadium |
| 2021-09-24 19:30:00September 24, 2021 | MTL | 27 - 30 | TOR | BMO Field |
| 2021-09-24 22:30:00September 24, 2021 | SSK | 31 - 24 | BC | BC Place |
| 2021-09-28 19:30:00September 28, 2021 | EDM | 24 - 34 | OTT | TD Place Stadium |
| 2021-10-01 20:00:00October 1, 2021 | WPG | 30 - 9 | BC | BC Place |
| 2021-10-02 16:00:00October 2, 2021 | MTL | 23 - 20 | HAM | Tim Hortons Field |
| 2021-10-02 19:00:00October 2, 2021 | SSK | 17 - 23 | CGY | McMahon Stadium |
| 2021-10-06 19:30:00October 6, 2021 | OTT | 16 - 35 | TOR | BMO Field |
| 2021-10-08 20:30:00October 8, 2021 | EDM | 3 - 30 | WPG | IG Field |
| 2021-10-09 19:00:00October 9, 2021 | CGY | 22 - 19 | SSK | Mosaic Stadium |
| 2021-10-11 13:00:00October 11, 2021 | OTT | 16 - 20 | MTL | |
| 2021-10-11 16:00:00October 11, 2021 | TOR | 24 - 23 | HAM | Tim Hortons Field |
| 2021-10-15 21:00:00October 15, 2021 | WPG | 26 - 16 | EDM | Commonwealth Stadium |
| 2021-10-16 16:00:00October 16, 2021 | MTL | 27 - 16 | OTT | TD Place Stadium |
| 2021-10-16 19:00:00October 16, 2021 | CGY | 39 - 10 | BC | BC Place |
| 2021-10-22 19:30:00October 22, 2021 | TOR | 16 - 37 | MTL | BMO Field |
| 2021-10-23 16:00:00October 23, 2021 | OTT | 3 - 32 | HAM | Tim Hortons Field |
| 2021-10-23 19:00:00October 23, 2021 | BC | 0 - 45 | WPG | IG Field |
| 2021-10-23 21:45:00October 23, 2021 | SSK | 20 - 17 | CGY | McMahon Stadium |
| 2021-10-29 19:00:00October 29, 2021 | CGY | 23 - 13 | OTT | TD Place Stadium |
| 2021-10-29 21:45:00October 29, 2021 | HAM | 39 - 23 | EDM | Commonwealth Stadium |
| 2021-10-30 16:00:00October 30, 2021 | BC | 29 - 31 | TOR | BMO Field |
| 2021-10-30 19:00:00October 30, 2021 | SSK | 19 - 14 | MTL | |
| 2021-11-05 19:00:00November 5, 2021 | BC | 18 - 26 | HAM | Tim Hortons Field |
| 2021-11-05 21:45:00November 5, 2021 | EDM | 19 - 17 | SSK | Mosaic Stadium |
| 2021-11-06 16:00:00November 6, 2021 | TOR | 23 - 20 | OTT | TD Place Stadium |
| 2021-11-06 19:00:00November 6, 2021 | MTL | 21 - 31 | WPG | IG Field |
| 2021-11-12 19:30:00November 12, 2021 | HAM | 12 - 31 | TOR | BMO Field |
| 2021-11-12 22:30:00November 12, 2021 | CGY | 33 - 23 | BC | BC Place |
| 2021-11-13 13:00:00November 13, 2021 | WPG | 14 - 28 | MTL | |
| 2021-11-13 16:00:00November 13, 2021 | EDM | 24 - 29 | SSK | TD Place Stadium |
| 2021-11-16 19:30:00November 16, 2021 | EDM | 13 - 7 | TOR | BMO Field |
| 2021-11-19 19:30:00November 19, 2021 | OTT | 19 - 18 | MTL | |
| 2021-11-19 22:30:00November 19, 2021 | EDM | 10 - 43 | BC | BC Place |
| 2021-11-20 16:00:00November 20, 2021 | SSK | 3 - 24 | HAM | Tim Hortons Field |
| 2021-11-20 19:00:00November 20, 2021 | WPG | 12 - 13 | CGY | McMahon Stadium |
