Billy Cannon has earned the most fantasy points in a game, with 63 points against the New York Titans on December 10, 1961.
| NAME | FPTS | DATE | TM | OPP | YDS | TD | RUSH YDS | RUSH TD | REC YDS | REC TD | KR YDS | KR TD | PR YDS | PR TD | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
 | Billy Cannon | 63 | 12/10/1961 |  HOU | @ |  NYT | 373 | 5 | 216 | 3 | 114 | 2 | 43 | 0 | 0 | 0 |
| | Gale Sayers | 56.2 | 12/12/1965 |  CHI | vs |  SF | 336 | 6 | 113 | 4 | 89 | 1 | 0 | 0 | 134 | 1 |
| | Clinton Portis | 55.4 | 12/7/2003 |  DEN | vs |  KC | 254 | 5 | 218 | 5 | 36 | 0 | 0 | 0 | 0 | 0 |
| | Cookie Gilchrist | 54.3 | 12/8/1963 |  BUF | vs | NYJ | 243 | 5 | 243 | 5 | 0 | 0 | 0 | 0 | 0 | 0 |
| | Abner Haynes | 54.2 | 11/26/1961 | DLT | vs |  OAK | 242 | 5 | 158 | 4 | 84 | 1 | 0 | 0 | 0 | 0 |
 | Alvin Kamara | 53.2 | 12/25/2020 |  NO | vs |  MIN | 172 | 6 | 155 | 6 | 17 | 0 | 0 | 0 | 0 | 0 |
| | Shaun Alexander | 53.1 | 9/29/2002 |  SEA | vs | MIN | 231 | 5 | 139 | 4 | 92 | 1 | 0 | 0 | 0 | 0 |
 | Jim Brown | 52.9 | 11/19/1961 |  CLE | vs |  PHI | 313 | 4 | 237 | 4 | 52 | 0 | 24 | 0 | 0 | 0 |
 | Jerry Rice | 52.5 | 10/14/1990 | SF | @ |  ATL | 225 | 5 | 0 | 0 | 225 | 5 | 0 | 0 | 0 | 0 |
| | Corey Dillon | 51.6 | 12/4/1997 |  CIN | vs | TEN | 276 | 4 | 246 | 4 | 30 | 0 | 0 | 0 | 0 | 0 |
| | Jamaal Charles | 51.5 | 12/15/2013 | KC | @ | OAK | 215 | 5 | 20 | 1 | 195 | 4 | 0 | 0 | 0 | 0 |
 | Doug Martin | 51.2 | 11/4/2012 |  TB | @ | OAK | 272 | 4 | 251 | 4 | 21 | 0 | 0 | 0 | 0 | 0 |
 | Joe Mixon | 51.1 | 11/6/2022 | CIN | vs |  CAR | 211 | 5 | 153 | 4 | 58 | 1 | 0 | 0 | 0 | 0 |
| | George Blanda | 50.7 | 11/19/1961 | HOU | vs | NYT | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| | Jerry Butler | 50.7 | 9/23/1979 | BUF | vs | NYJ | 267 | 4 | 12 | 0 | 255 | 4 | 0 | 0 | 0 | 0 |
 | Jonathan Taylor | 50.4 | 11/21/2021 |  IND | @ | BUF | 204 | 5 | 185 | 4 | 19 | 1 | 0 | 0 | 0 | 0 |
| | Mike Anderson | 49.6 | 12/3/2000 | DEN | @ | NO | 256 | 4 | 251 | 4 | 5 | 0 | 0 | 0 | 0 | 0 |
| | Larry Brown | 49.5 | 12/16/1973 |  WAS | vs | PHI | 255 | 4 | 150 | 1 | 105 | 3 | 0 | 0 | 0 | 0 |
 | Michael Vick | 49.3 | 11/15/2010 | PHI | @ | WAS | 80 | 2 | 80 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
 | Barry Sanders | 49.1 | 11/24/1991 |  DET | @ | MIN | 251 | 4 | 220 | 4 | 31 | 0 | 0 | 0 | 0 | 0 |
| | Fred Taylor | 48.8 | 11/19/2000 |  JAX | @ |  PIT | 248 | 4 | 234 | 3 | 14 | 1 | 0 | 0 | 0 | 0 |
| | Priest Holmes | 48.7 | 11/24/2002 | KC | @ | SEA | 307 | 3 | 197 | 2 | 110 | 1 | 0 | 0 | 0 | 0 |
| | Art Powell | 48.7 | 12/22/1963 | OAK | vs | HOU | 247 | 4 | 0 | 0 | 247 | 4 | 0 | 0 | 0 | 0 |
| | Y.A. Tittle | 48.3 | 10/28/1962 |  NYG | vs | WAS | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| | Mark Rypien | 48.1 | 11/10/1991 | WAS | vs | ATL | 4 | 1 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
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