Mike Edwards, Rasul Douglas and Trevon Diggs shared the NFL lead in pick sixes in 2021 with 2.
Next came Kyle Van Noy (1) and DeMarcus Lawrence (1) — the full top 50 is ranked below with team and position.
| Rank | Player | Team | Position | Pick Sixes |
|---|---|---|---|---|
| 1 | Mike Edwards | KC | S | 2 |
| 2 | Rasul Douglas | MIA | CB | 2 |
| 3 | Trevon Diggs | DAL | CB | 2 |
| 4 | Kyle Van Noy | BAL | LB | 1 |
| 5 | DeMarcus Lawrence | SEA | LB | 1 |
| 6 | Roquan Smith | BAL | LB | 1 |
| 7 | P.J. Williams | NO | UNK | 1 |
| 8 | Malcolm Jenkins | NO | S | 1 |
| 9 | Tyrann Mathieu | KC | UNK | 1 |
| 10 | Micah Hyde | BUF | UNK | 1 |
| 11 | Daniel Sorensen | KC | UNK | 1 |
| 12 | Kevin Byard | NE | S | 1 |
| 13 | Nick Vigil | DAL | UNK | 1 |
| 14 | Carlos Watkins | TEN | DE | 1 |
| 15 | Xavien Howard | IND | CB | 1 |
| 16 | Elandon Roberts | LV | LB | 1 |
| 17 | Chuck Clark | DET | S | 1 |
| 18 | Cole Holcomb | PIT | LB | 1 |
| 19 | Nik Needham | NYJ | CB | 1 |
| 20 | Marlon Davidson | HOU | DT | 1 |
| 21 | Denzel Ward | CLE | CB | 1 |
| 22 | Byron Murphy Jr. | MIN | CB | 1 |
| 23 | Patrick Peterson | MIN | UNK | 1 |
| 24 | Darius Slay | BUF | CB | 1 |
| 25 | Jimmie Ward | HOU | S | 1 |