| # | Squadra | PG | V | P | S | GF | GC | DG | Pts. |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Philadelphia Union | 32 | 18 | 10 | 4 | 68 | 22 | +46 | 64 |
| 2 | Montréal | 32 | 18 | 5 | 9 | 59 | 49 | +10 | 59 |
| 3 | New York RB | 32 | 14 | 8 | 10 | 47 | 39 | +8 | 50 |
| 4 | New York City | 32 | 14 | 7 | 11 | 53 | 39 | +14 | 49 |
| 5 | Orlando City | 31 | 13 | 6 | 12 | 40 | 46 | -6 | 45 |
| 6 | Cincinnati | 31 | 11 | 12 | 8 | 56 | 50 | +6 | 45 |
| 7 | Inter Miami | 31 | 12 | 6 | 13 | 41 | 52 | -11 | 42 |
| 8 | Columbus Crew | 31 | 9 | 15 | 7 | 41 | 36 | +5 | 42 |
| 9 | Atlanta United | 32 | 10 | 10 | 12 | 46 | 50 | -4 | 40 |
| 10 | Charlotte | 31 | 12 | 2 | 17 | 38 | 48 | -10 | 38 |
| 11 | New England | 32 | 9 | 11 | 12 | 44 | 48 | -4 | 38 |
| 12 | Chicago Fire | 32 | 9 | 8 | 15 | 35 | 45 | -10 | 35 |
| 13 | Toronto | 32 | 9 | 7 | 16 | 49 | 61 | -12 | 34 |
| 14 | D.C. United | 32 | 7 | 6 | 19 | 34 | 65 | -31 | 27 |
| 2022. Settembre 28. mercoledì | ||
| Seattle Sounders | 03:00 | Cincinnati |
| 2022. Ottobre 1. sabato | ||
| Toronto | 00:30 | Inter Miami |
| New England | 18:30 | Atlanta United |
| Colorado Rapids | 20:30 | Dallas |
| Charlotte | 22:30 | Philadelphia Union |
| 2022. Ottobre 2. domenica | ||
| Cincinnati | 00:30 | Chicago Fire |
| Columbus Crew | 00:30 | New York RB |
| Montréal | 00:30 | D.C. United |
| Vancouver Whitecaps FC | 03:00 | Austin |
| SJ Earthquakes | 03:00 | Minnesota United |
| LA Galaxy | 03:30 | Real Salt Lake |
| New York City | 18:00 | Orlando City |
| Portland Timbers | 20:00 | Los Angeles |
| Sporting KC | 22:00 | Seattle Sounders |
| 2022. Ottobre 3. lunedì | ||
| Nashville SC | 01:30 | Houston Dynamo |
| 2022. Ottobre 6. giovedì | ||
| Charlotte | 00:00 | Columbus Crew |
| Inter Miami | 01:00 | Orlando City |
| 2022. Settembre 25. domenica | ||
| SJ Earthquakes | 2 - 3 | LA Galaxy |
| 2022. Settembre 19. lunedì | ||
| Los Angeles | 3 - 1 | Houston Dynamo |
| 2022. Settembre 18. domenica | ||
| D.C. United | 2 - 3 | Inter Miami |
| Columbus Crew | 1 - 1 | Portland Timbers |
| SJ Earthquakes | 1 - 1 | Dallas |
| LA Galaxy | 4 - 1 | Colorado Rapids |
| Vancouver Whitecaps FC | 2 - 1 | Seattle Sounders |
| Real Salt Lake | 1 - 2 | Cincinnati |
| Austin | 1 - 1 | Nashville SC |
| Sporting KC | 4 - 1 | Minnesota United |
| Chicago Fire | 2 - 3 | Charlotte |
| New England | 0 - 1 | Montréal |
| Orlando City | 4 - 0 | Toronto |
| 2022. Settembre 17. sabato | ||
| Atlanta United | 0 - 0 | Philadelphia Union |
| New York City | 2 - 0 | New York RB |
| 2022. Settembre 15. giovedì | ||
| Vancouver Whitecaps FC | 3 - 0 | LA Galaxy |
| Colorado Rapids | 2 - 1 | SJ Earthquakes |
| Austin | 3 - 0 | Real Salt Lake |
| 2022. Settembre 14. mercoledì | ||
| Orlando City | 0 - 1 | Atlanta United |
