Linney appeared in minor roles in a few early 1990s films, including Dave in 1993, before coming to prominence in the public television mini-series Tales of the City. She was then cast in a series of high-profile thrillers, including Congo, Primal Fear and Absolute Power. She made her Hollywood breakthrough in 1998 when she was cast as Jim Carrey's wife in The Truman Show, for which she received much critical acclaim.

In 2000, she was nominated for an Academy Award for Best Actress for her role in the lower-budget film You Can Count on Me. That same year she also appeared in the role of an artist's model in the low budget, critically praised film Maze with Rob Morrow. In 2003, Linney appeared in several notable films, including Mystic River, Love Actually and The Life of David Gale. Her 2004 performance in Kinsey, as the title character's wife, was nominated for the Academy Award for Best Supporting Actress.

In 2005, Linney starred in horror film The Exorcism of Emily Rose, and the comedy-drama The Squid and the Whale, for which she received a Golden Globe nomination for "Best Performance by an Actress in a Motion Picture - Musical or Comedy". In 2006, Linney appeared in the political satire Man of the Year, in the comedy Driving Lessons (starring Rupert Grint of Harry Potter fame), and also in the Australian drama Jindabyne by Ray Lawrence. Jindabyne is based on Raymond Carver´s short novel So much water so close to home.

In 2007, Linney appeared in the spy thriller Breach, The Nanny Diaries, opposite Scarlett Johansson and based on the book by Emma McLaughlin and Nicola Kraus, and The Savages, where Linney and Philip Seymour Hoffman played siblings. She received her third Academy Award nomination for this film—this time as Best Actress. Recently, the actress starred in The Other Man, a film where she plays beside Antonio Banderas and Liam Neeson, who she had acted alongside in Kinsey.

• Kevin Approaches (2009) (in production) (rumored)
  
• The Other Man (2008) .... Lisa
• "John Adams" .... Abigail Adams (7 episodes, 2008)
       - Join or Die (2008) TV episode .... Abigail Adams
       - Peacefield (2008) TV episode .... Abigail Adams
       - Unnecessary War (2008) TV episode .... Abigail Adams
       - Unite or Die (2008) TV episode .... Abigail Adams
       - Reunion (2008) TV episode .... Abigail Adams
        (2 more)
• The City of Your Final Destination (2007) .... Caroline
• The Nanny Diaries (2007) .... Mrs. X
• Breach (2007) .... Kate Burroughs
• The Savages (2007) .... Wendy Savage
• Man of the Year (2006) .... Eleanor Green
• The Hottest State (2006) .... Jesse
• Jindabyne (2006) .... Claire
• "The American Experience" .... Narrator (2 episodes, 2005-2006)
       - Annie Oakley (2006) TV episode (voice) .... Narrator
       - Mary Pickford (2005) TV episode (voice) .... Narrator
• "American Dad!" (1 episode, 2006)
       - Roger n' Me (2006) TV episode (voice)
• Driving Lessons (2006) .... Laura Marshall
• The Exorcism of Emily Rose (2005) .... Erin Bruner
• The Squid and the Whale (2005) .... Joan Berkman
• Kinsey (2004) .... Clara McMillen
• P.S. (2004) .... Louise Harrington
• "Frasier" .... Charlotte / ... (6 episodes, 2003-2004)
       - Goodnight, Seattle: Part 1 (2004) TV episode .... Charlotte
       - Detour (2004) TV episode .... Charlotte
       - And Frasier Makes Three (2004) TV episode .... Charlotte
       - Miss Right Now (2004) TV episode .... Charlotte
       - Match Game (2004) TV episode .... Charlotte
        (1 more)
• Love Actually (2003) .... Sarah
• Mystic River (2003) .... Annabeth Markum
• The Life of David Gale (2003) .... Constance Harraway
  ... aka Das Leben des David Gale (Germany)