Standing
| # | Team | MP | W | D | L | F | A | G | P |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Philadelphia Union | 33 | 18 | 10 | 5 | 68 | 26 | +42 | 64 |
| 2 | Montréal | 33 | 19 | 5 | 9 | 60 | 49 | +11 | 62 |
| 3 | New York RB | 33 | 14 | 8 | 11 | 48 | 41 | +7 | 50 |
| 4 | New York City | 32 | 14 | 7 | 11 | 53 | 39 | +14 | 49 |
| 5 | Cincinnati | 33 | 11 | 13 | 9 | 59 | 54 | +5 | 46 |
| 6 | Orlando City | 31 | 13 | 6 | 12 | 40 | 46 | -6 | 45 |
| 7 | Inter Miami | 32 | 13 | 6 | 13 | 42 | 52 | -10 | 45 |
| 8 | Columbus Crew | 32 | 10 | 15 | 7 | 43 | 37 | +6 | 45 |
| 9 | Charlotte | 32 | 13 | 2 | 17 | 42 | 48 | -6 | 41 |
| 10 | New England | 33 | 10 | 11 | 12 | 46 | 49 | -3 | 41 |
| 11 | Atlanta United | 33 | 10 | 10 | 13 | 47 | 52 | -5 | 40 |
| 12 | Chicago Fire | 33 | 10 | 8 | 15 | 38 | 47 | -9 | 38 |
| 13 | Toronto | 33 | 9 | 7 | 17 | 49 | 62 | -13 | 34 |
| 14 | D.C. United | 33 | 7 | 6 | 20 | 34 | 66 | -32 | 27 |
Fixtures
| October 2, 2022 | ||
| New York City | 20:00 | Orlando City |
| Portland Timbers | 22:00 | Los Angeles |
| October 3, 2022 | ||
| Sporting KC | 00:00 | Seattle Sounders |
| Nashville SC | 03:30 | Houston Dynamo |
| October 6, 2022 | ||
| Charlotte | 02:00 | Columbus Crew |
| Inter Miami | 03:00 | Orlando City |
| October 9, 2022 | ||
| Atlanta United | 21:30 | New York City |
| Chicago Fire | 21:30 | New England |
| D.C. United | 21:30 | Cincinnati |
| Inter Miami | 21:30 | Montréal |
| New York RB | 21:30 | Charlotte |
| Orlando City | 21:30 | Columbus Crew |
| Philadelphia Union | 21:30 | Toronto |
| October 10, 2022 | ||
| Seattle Sounders | 00:00 | SJ Earthquakes |
| Real Salt Lake | 00:00 | Portland Timbers |
| Minnesota United | 00:00 | Vancouver Whitecaps FC |
| Los Angeles | 00:00 | Nashville SC |
| Houston Dynamo | 00:00 | LA Galaxy |
| Dallas | 00:00 | Sporting KC |
| Austin | 00:00 | Colorado Rapids |
Result
| October 2, 2022 | ||
| LA Galaxy | 1 - 1 | Real Salt Lake |
| Vancouver Whitecaps FC | 2 - 0 | Austin |
| SJ Earthquakes | 2 - 0 | Minnesota United |
| Montréal | 1 - 0 | D.C. United |
| Columbus Crew | 2 - 1 | New York RB |
| Cincinnati | 2 - 3 | Chicago Fire |
| Charlotte | 4 - 0 | Philadelphia Union |
| October 1, 2022 | ||
| Colorado Rapids | 1 - 0 | Dallas |
| New England | 2 - 1 | Atlanta United |
| Toronto | 0 - 1 | Inter Miami |
| September 28, 2022 | ||
| Seattle Sounders | 1 - 1 | Cincinnati |
| September 25, 2022 | ||
| SJ Earthquakes | 2 - 3 | LA Galaxy |
| September 19, 2022 | ||
| Los Angeles | 3 - 1 | Houston Dynamo |