| 1992 | Where the Day Takes You | Manny | |
| 1993 | Made in America | Tea Cake Walters | |
| 1993 | Six Degrees of Separation | Paul | |
| 1995 | Bad Boys | Detective Mike Lowrey | |
| 1996 | Independence Day | Captain Steven "Steve" Hiller, USMC | |
| 1997 | Men in Black | James Darrell Edwards / Agent J | |
| 1998 | Enemy of the State | Robert Clayton Dean | |
| 1999 | Wild Wild West | Captain James "Jim" West | |
| 2000 | The Legend of Bagger Vance | Bagger Vance | |
| 2001 | Ali | Muhammad Ali | |
| 2002 | Men in Black II | James Darrell Edwards / Agent J | |
| 2003 | Bad Boys II | Detective Mike Lowrey | |
| 2004 | Jersey Girl | Himself | Cameo appearance |
| 2004 | I, Robot | Detective Del Spooner | Producer |
| 2004 | Shark Tale | Oscar | Voice only |
| 2005 | Hitch | Alex "Hitch" Hitchens | Also producer |
| 2006 | The Pursuit of Happyness | Chris Gardner | Also producer |
| 2007 | I Am Legend | Dr. Robert Neville | Also producer |
| 2008 | Hancock | John Hancock | Also producer |
| 2008 | Seven Pounds | Tim Thomas | Also producer |
| 2012 | Men in Black 3 | James Darrell Edwards / Agent J | |
| 2013 | After Earth | Cypher Raige | Also writer (story) and producer |
| 2013 | Anchorman 2: The Legend Continues | Jeff Bullington | Cameo appearance |
| 2014 | Winter's Tale | Judge | |
| 2015 | Focus | Nicky Spurgeon | |
| 2015 | Concussion | Dr. Bennet Omalu | In post-production |
| 2016 | Suicide Squad | Floyd Lawton / Deadshot | Filming |