| Year | Film | Role | Notes |
| 1982 | Lookin' to Get Out | Tosh |
|
| 1993 | "Angela & Viril" | Angela | 2 minute short film |
| "Alice & Viril" | Alice | 2 minute short film |
| Cyborg 2 | Casella "Cash" Reese |
|
| 1995 | Without Evidence | Jodie Swearingen |
|
| Hackers | Kate "Acid Burn" Libby |
|
| 1996 | Mojave Moon | Eleanor "Elie" Rigby |
|
| Love Is All There Is | Gina Malacici |
|
| Foxfire | Margret "Legs" Sadovsky |
|
| 1997 | True Women (TV) | Georgia Virginia Lawshe Woods |
|
| George Wallace (TV) | Cornelia Wallace | Golden Globe Award for Best Supporting Actress – Series/Miniseries/TV Movie Nominated – Emmy Award for Best Supporting Actress in a Miniseries or a Movie |
| Playing God | Claire |
|
| 1998 | Gia (TV) | Gia Marie Carangi | Golden Globe Award for Best Actress in a Mini-Series or Motion Picture Made for TV Screen Actors Guild Award for Best Actress in a TV Movie or Miniseries Nominated – Emmy Award for Best Actress in a Miniseries or a Movie |
| Hell's Kitchen | Gloria McNeary |
|
| Playing by Heart | Joan | National Board of Review Award – Breakthrough Performance |
| Pushing Tin | Mary Bell |
|
| 1999 | The Bone Collector | Amelia Donaghy |
|
| Girl, Interrupted | Lisa Rowe | Academy Award for Best Supporting Actress Broadcast Film Critics Association Award for Best Supporting Actress Golden Globe Award for Best Supporting Actress – Motion Picture Screen Actors Guild Award for Best Supporting Actress – Motion Picture Nominated – Chicago Film Critics Association Award for Best Supporting Actress |
| 2000 | Gone in Sixty Seconds | Sara "Sway" Wayland |
|
| 2001 | Lara Croft: Tomb Raider | Lara Croft | Nominated — MTV Movie Award for Best Female Performance Nominated — MTV Movie Award for Best Fight |
| Original Sin | Julia Russell |
|
| 2002 | Life or Something Like It | Lanie Kerrigan |
|
| 2003 | Lara Croft Tomb Raider: The Cradle of Life | Lara Croft |
|
| Beyond Borders | Sarah Jordan |
|
| 2004 | Taking Lives | Illeana Scott |
|
| Shark Tale | Lola | Voice |
| Sky Captain and the World of Tomorrow | Francesca "Franky" Cook | People's Choice Award – Favorite Female Action Star |
| The Fever (TV) | Revolutionary | Cameo |
| Alexander | Olympias |
|
| 2005 | Mr. & Mrs. Smith | Jane Smith | MTV Movie Award for Best Fight Nominated – MTV Movie Award for Best Kiss Nominated – People's Choice Award – Favorite Female Movie Star Nominated – People's Choice Award – Favorite Female Action Star Nominated – People's Choice Award – Favorite On-Screen Match-Up (with Brad Pitt) |
| 2006 | The Good Shepherd | Margaret Russell |
|
| 2007 | A Mighty Heart | Mariane Pearl | Nominated – Broadcast Film Critics Association Award for Best Actress Nominated – Chicago Film Critics Association Award for Best Actress Nominated – Golden Globe Award for Best Actress – Motion Picture Drama Nominated – Independent Spirit Award for Best Lead Female Nominated – London Film Critics Circle Award for Best Actress Nominated – Online Film Critics Society Award for Best Actress Nominated – Screen Actors Guild Award for Best Actress – Motion Picture |
| Beowulf | Grendel's mother | Nominated – MTV Movie Award for Best Villain |
| 2008 | Kung Fu Panda | Master Tigress | Voice |
| Wanted | Fox | People's Choice Award – Favorite Female Action Star Nominated – People's Choice Award – Favorite Female Movie Star Nominated — MTV Movie Award for Best Female Performance Nominated — MTV Movie Award for Best Kiss Nominated — MTV Movie Award for Best WTF Moment |
| Changeling | Christine Collins | Saturn Award for Best Actress Nominated – Academy Award for Best Actress Nominated – BAFTA Award for Best Actress in a Leading Role Nominated – Broadcast Film Critics Association Award for Best Actress Nominated – Chicago Film Critics Association Award for Best Actress Nominated – Golden Globe Award for Best Actress – Motion Picture Drama Nominated – London Film Critics Circle Award for Best Actress Nominated – Screen Actors Guild Award for Best Actress – Motion Picture |
| 2010 | Salt | Evelyn Salt | (in production) |
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