Hudson's breakthrough was as Penny Lane in Cameron Crowe's Almost Famous (2000), for which she received an Academy Award nomination for Best Supporting Actress and won the Golden Globe Award for Best Supporting Actress. She had previously appeared in the lesser-known films Gossip, a teenage drama, and 200 Cigarettes, a New Year's-set comedy with a large cast of actors. Regarding her early career and success, Hudson has noted that she is a "hard worker", and did not want to be associated with her well-known parents, wishing to avoid the perception that she "rode on somebody's coattails". In 2002 Hudson starred in the remake of the historical romance The Four Feathers, a film which was not well received by critics or audiences. Her next film, How to Lose a Guy in 10 Days, a romantic comedy, became a big success at the box office, grossing over $100 million after its February 2003 release. Hudson subsequently appeared in several romantic comedies, including Alex and Emma and Raising Helen; the films met with varying degrees of success.

Hudson headlined a thriller called The Skeleton Key in 2005. The film, which had a production budget of $43 million, enjoyed box office success, grossing over $91.9 million worldwide ($47.9 million in North America). Her later film, a comedy titled You, Me and Dupree and co-starring Owen Wilson and Matt Dillon, grossed $21.5 million on its opening weekend of July 14, 2006. In 2007 Hudson directed the short film Cutlass, one of Glamour magazine's "Reel Moments" based on readers' personal essays. Cutlass co-stars Kurt Russell, Dakota Fanning, Virginia Madsen, Chevy Chase and Kristen Stewart.

In 2008, she appeared in Fool's Gold, a romantic comedy released on February 8th, and her second film to co-star Matthew McConaughey. She had been certified in scuba diving in the Great Barrier Reef for the movie's underwater scenes. Her latest film, another romantic comedy, titled My Best Friend's Girl, was released in September. It was recently announced that Hudson will appear in the musical film Nine alongside Daniel Day-Lewis, Marion Cotillard, Penelope Cruz, Nicole Kidman and Judi Dench, among others. The film, directed by Rob Marshall, will be released in the fall of 2009.

• Big Eyes (2009) (pre-production) .... Margaret Keane
• The Killer Inside Me (2010) (filming) .... Amy Stanton
• Nine (2009) (post-production) .... Stephanie Necrophuros
  
• Bride Wars (2009) .... Liv
• My Best Friend's Girl (2008) .... Alexis
• Fool's Gold (2008/I) .... Tess Finnegan
• You, Me and Dupree (2006) .... Molly
• The Skeleton Key (2005) .... Caroline Ellis
• Raising Helen (2004) .... Helen Harris
• Le divorce (2003) .... Isabel Walker
• Alex & Emma (2003) .... Emma Dinsmore / Ylva / Elsa / Eldora / Anna
• How to Lose a Guy in 10 Days (2003) .... Andie
  ... aka Wie werde ich ihn los in 10 Tagen (Germany)
• The Four Feathers (2002) .... Ethne Eustace
• The Cutting Room (2001) (uncredited) .... Chrissie Campbell
• Dr T and the Women (2000) .... Dee Dee
  ... aka Dr. T and the Women (Germany) (USA: alternative spelling)
• Almost Famous (2000) .... Penny Lane
  ... aka Untitled: Almost Famous the Bootleg Cut (USA: director's cut (DVD title))
• Gossip (2000/I) .... Naomi Preston
• About Adam (2000) .... Lucy Owens
  
• 200 Cigarettes (1999) .... Cindy
• Desert Blue (1998) .... Skye Davidson
• Ricochet River (1998) .... Lorna
• "EZ Streets" .... Larraine Cahill (1 episode, 1997)
       - Neither Have I Wings to Fly (1997) TV episode .... Larraine Cahill
• "Party of Five" .... Cory (1 episode, 1996)
       - Spring Breaks: Part 1 (1996) TV episode .... Cory