| 2021-09-12 | 1 | vs |  CLE | 33-29 | W | 5.5 | 54.5 | GEHA Field at Arrowhead Stadium |
| 2021-09-19 | 2 | @ |  BAL | 35-36 | L | -3.5 | 53.5 | M&T Bank Stadium |
| 2021-09-26 | 3 | vs |  LAC | 24-30 | L | 6.5 | 55 | GEHA Field at Arrowhead Stadium |
| 2021-10-03 | 4 | @ |  PHI | 42-30 | W | -7.5 | 53.5 | Lincoln Financial Field |
| 2021-10-10 | 5 | vs |  BUF | 20-38 | L | 2.5 | 57 | GEHA Field at Arrowhead Stadium |
| 2021-10-17 | 6 | @ |  WAS | 31-13 | W | -6 | 54 | FedExField |
| 2021-10-24 | 7 | @ |  TEN | 3-27 | L | -4 | 57.5 | Nissan Stadium |
| 2021-11-01 | 8 | vs |  NYG | 20-17 | W | 10.5 | 53 | GEHA Field at Arrowhead Stadium |
| 2021-11-07 | 9 | vs |  GB | 13-7 | W | 7 | 48 | GEHA Field at Arrowhead Stadium |
| 2021-11-14 | 10 | @ |  LV | 41-14 | W | -2.5 | 53.5 | Allegiant Stadium |
| 2021-11-21 | 11 | vs |  DAL | 19-9 | W | 2.5 | 56 | GEHA Field at Arrowhead Stadium |
| 2021-12-05 | 13 | vs |  DEN | 22-9 | W | 8.5 | 46.5 | GEHA Field at Arrowhead Stadium |
| 2021-12-12 | 14 | vs | LV | 48-9 | W | 10 | 48 | GEHA Field at Arrowhead Stadium |
| 2021-12-16 | 15 | @ | LAC | 34-28 | W | -3 | 54 | SoFi Stadium |
| 2021-12-26 | 16 | vs |  PIT | 36-10 | W | 10.5 | 44 | GEHA Field at Arrowhead Stadium |
| 2022-01-02 | 17 | @ |  CIN | 31-34 | L | -3.5 | 51 | Paul Brown Stadium |
| 2022-01-08 | 18 | @ | DEN | 28-24 | W | -11.5 | 44.5 | Empower Field at Mile High |
| 2022-01-16 | 19 | vs | PIT | 42-21 | W | 13 | 46 | GEHA Field at Arrowhead Stadium |
| 2022-01-23 | 20 | vs | BUF | 42-36 | W | 2.5 | 54 | GEHA Field at Arrowhead Stadium |
| 2022-01-30 | 21 | vs | CIN | 24-27 | L | 7 | 54.5 | GEHA Field at Arrowhead Stadium |
