| 1. | Maurice Jones-Drew (24) | 22.1 | Jacksonville Jaguars vs. Tennessee Titans, November 1, 2009 |
| 2. | Michael Vick (22) | 17.3 | Atlanta Falcons vs. Minnesota Vikings, December 1, 2002 |
| 3. | Paul Lowe | 17.1 | Los Angeles Chargers vs. Boston Patriots, October 28, 1960 |
| 4. | Napoleon Kaufman | 16.6 | Oakland Raiders vs. San Diego Chargers, September 22, 1996 |
| 5. | Tim Biakabutuka | 16.5 | Carolina Panthers vs. Cincinnati Bengals, September 26, 1999 |
| 6. | Johnny Morris | 16.3 | Chicago Bears vs. San Francisco 49ers, October 16, 1960 |
| 7. | Elmer Angsman | 15.9 | Chicago Cardinals vs. Philadelphia Eagles, December 28, 1947 |
| Fred Taylor | 15.9 | Jacksonville Jaguars vs. Oakland Raiders, December 23, 2007 |
| 9. | Keith Lincoln | 15.8 | San Diego Chargers vs. Boston Patriots, January 5, 1964 |
| 10. | Fred Ford | 15.6 | Los Angeles Chargers vs. New York Titans, December 18, 1960 |
| Jack Spikes | 15.6 | Dallas Texans vs. San Diego Chargers, September 10, 1961 |
| Joe Webb (25) | 15.6 | Minnesota Vikings vs. Detroit Lions, December 11, 2011 |
| 13. | Randall Cunningham | 15.5 | Philadelphia Eagles vs. New England Patriots, November 4, 1990 |
| 14. | Stump Mitchell | 15.4 | St. Louis Cardinals vs. San Francisco 49ers, September 18, 1983 |
| 15. | Napoleon Kaufman | 15.3 | Oakland Raiders vs. Tampa Bay Buccaneers, December 19, 1999 |
| 16. | Leroy Harris | 15.2 | Philadelphia Eagles vs. Green Bay Packers, November 25, 1979 |
| 17. | DeShawn Wynn | 15.1 | Green Bay Packers vs. Detroit Lions, December 28, 2008 |
| 18. | Vinny Testaverde | 15.0 | Tampa Bay Buccaneers vs. Minnesota Vikings, December 16, 1990 |
| 19. | Larry Johnson | 14.9 | Kansas City Chiefs vs. Tennessee Titans, December 13, 2004 |
| Thomas Jones | 14.9 | Tampa Bay Buccaneers vs. Green Bay Packers, November 16, 2003 |
| Michael Vick (24) | 14.9 | Atlanta Falcons vs. St. Louis Rams, January 15, 2005 |
| 22. | Steve Grogan | 14.7 | New England Patriots vs. New York Jets, October 18, 1976 |
| Kordell Stewart | 14.7 | Pittsburgh Steelers vs. Cincinnati Bengals, October 11, 1998 |
| Michael Turner (25) | 14.7 | San Diego Chargers vs. Denver Broncos, October 7, 2007 |
| 25. | Bo Jackson | 14.6 | Los Angeles Raiders vs. Cincinnati Bengals, December 16, 1990 |
| Kordell Stewart | 14.6 | Pittsburgh Steelers vs. Carolina Panthers, December 22, 1996 |
| Fred Taylor | 14.6 | Jacksonville Jaguars vs. Indianapolis Colts, December 10, 2006 |
| Brian Westbrook | 14.6 | Philadelphia Eagles vs. San Francisco 49ers, September 24, 2006 |
| 29. | Abner Haynes | 14.3 | Dallas Texans vs. New York Titans, November 24, 1960 |
| Derrick Ward | 14.3 | New York Giants vs. Carolina Panthers, December 21, 2008 |
| 31. | Dick Bass | 14.1 | Los Angeles Rams vs. Minnesota Vikings, December 3, 1961 |
| Essex Johnson | 14.1 | Cincinnati Bengals vs. Philadelphia Eagles, September 19, 1971 |
| Michael Turner (23) | 14.1 | San Diego Chargers vs. Indianapolis Colts, December 18, 2005 |
| 34. | Ron Dayne | 14.0 | Denver Broncos vs. Dallas Cowboys, November 24, 2005 |
| 35. | Tiki Barber | 13.9 | New York Giants vs. Philadelphia Eagles, September 12, 2004 |
| Ernie Green | 13.9 | Cleveland Browns vs. Dallas Cowboys, November 24, 1963 |
| 37. | Keith Lincoln | 13.8 | San Diego Chargers vs. Oakland Raiders, September 30, 1962 |
| Michael Vick (26) | 13.8 | Atlanta Falcons vs. New Orleans Saints, November 26, 2006 |
| 39. | Felix Jones (22) | 13.7 | Dallas Cowboys vs. New York Giants, September 20, 2009 |
| 40. | Napoleon Kaufman | 13.6 | Oakland Raiders vs. Kansas City Chiefs, December 9, 1996 |
| Terry Metcalf | 13.6 | St. Louis Cardinals vs. Washington Redskins, September 22, 1974 |
| Jahvid Best | 13.6 | Detroit Lions vs. Chicago Bears, October 10, 2011 |
| 43. | Wray Carlton | 13.5 | Buffalo Bills vs. Houston Oilers, December 5, 1965 |
| Willis McGahee (27) | 13.5 | Baltimore Ravens vs. Dallas Cowboys, December 20, 2008 |
| Terdell Middleton | 13.5 | Green Bay Packers vs. Detroit Lions, October 1, 1978 |
| 46. | Barry Foster | 13.4 | Pittsburgh Steelers vs. Buffalo Bills, September 8, 1991 |
| Donovan McNabb | 13.4 | Philadelphia Eagles vs. New York Giants, October 28, 2002 |
| 48. | Charlie Garner | 13.3 | Philadelphia Eagles vs. Washington Redskins, October 8, 1995 |
| 49. | Rock Cartwright | 13.1 | Washington Redskins vs. St. Louis Rams, December 4, 2005 |
| Bruce Harper | 13.1 | New York Jets vs. Buffalo Bills, October 3, 1983 |
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