2021 Main
Western Conference
| Pl | W | D | L | Diff | Pts | |||
| 1 | Phoenix Rising | 32 | 20 | 7 | 5 | 68:35 | 33 | 67 |
| 2 | El Paso | 32 | 18 | 10 | 4 | 56:34 | 22 | 64 |
| 3 | Orange County SC | 32 | 15 | 7 | 10 | 44:37 | 7 | 52 |
| 4 | San Antonio | 32 | 14 | 10 | 8 | 50:38 | 12 | 52 |
| 5 | Colorado Springs | 32 | 13 | 10 | 9 | 60:50 | 10 | 49 |
| 6 | San Diego Loyal | 32 | 14 | 6 | 12 | 51:43 | 8 | 48 |
| 7 | Rio Grande | 32 | 13 | 8 | 11 | 49:42 | 7 | 47 |
| 8 | New Mexico | 32 | 12 | 10 | 10 | 44:40 | 4 | 46 |
| 9 | Austin Bold | 32 | 10 | 12 | 10 | 32:42 | -10 | 42 |
| 10 | Oakland Roots | 32 | 11 | 8 | 13 | 36:43 | -7 | 41 |
| 11 | LA Galaxy 2 | 32 | 11 | 6 | 15 | 55:57 | -2 | 39 |
| 12 | Tacoma Defiance | 32 | 10 | 9 | 13 | 37:41 | -4 | 39 |
| 13 | Sacramento Republic | 32 | 8 | 12 | 12 | 36:42 | -6 | 36 |
| 14 | Real Monarchs | 32 | 5 | 7 | 20 | 28:56 | -28 | 22 |
| 15 | Las Vegas Lights | 32 | 6 | 3 | 23 | 41:77 | -36 | 21 |
Eastern Conference
| Pl | W | D | L | Diff | Pts | |||
| 1 | Tampa Bay | 32 | 23 | 2 | 7 | 55:23 | 32 | 71 |
| 2 | Louisville City | 32 | 18 | 7 | 7 | 61:37 | 24 | 61 |
| 3 | Birmingham | 32 | 18 | 6 | 8 | 51:31 | 20 | 60 |
| 4 | Charlotte Independ | 32 | 18 | 5 | 9 | 57:36 | 21 | 59 |
| 5 | Pittsburgh | 32 | 17 | 7 | 8 | 52:34 | 18 | 58 |
| 6 | Miami FC | 32 | 16 | 6 | 10 | 55:40 | 15 | 54 |
| 7 | Memphis | 32 | 14 | 8 | 10 | 47:42 | 5 | 50 |
| 8 | FC Tulsa | 32 | 14 | 5 | 13 | 49:48 | 1 | 47 |
| 9 | Hartford Athletic | 32 | 12 | 5 | 15 | 50:50 | 0 | 41 |
| 10 | Charleston | 32 | 10 | 7 | 15 | 49:60 | -11 | 37 |
| 11 | Oklahoma City Energy | 32 | 8 | 13 | 11 | 30:38 | -8 | 37 |
| 12 | Indy Eleven | 32 | 9 | 8 | 15 | 32:47 | -15 | 35 |
| 13 | Atlanta United 2 | 32 | 8 | 10 | 14 | 47:56 | -9 | 34 |
| 14 | New York Red Bulls 2 | 32 | 7 | 7 | 18 | 42:67 | -25 | 28 |
| 15 | Sporting Kansas City II | 32 | 4 | 8 | 20 | 33:64 | -31 | 20 |
| 16 | Loudoun | 32 | 4 | 3 | 25 | 31:78 | -47 | 15 |
2021 Play Offs
1/8-finals
Quarter-finals
| 1 | Tampa Bay | Birmingham | 1 : 0 |
| 2 | Louisville City | Charlotte Independ. | 1 : 0 |
| 3 | Orange County SC | Oakland Roots | 1 : 0 |
| 4 | San Antonio | Rio Grande | 3 : 1 |
Semi-finals
| 1 | Tampa Bay | Louisville City | 3 : 2 |
| 2 | Orange County SC | San Antonio | 2 : 1 |
Final
| 1 | Tampa Bay | Orange County SC | 1 : 3 |
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