Kinnear has appeared in many popular films, including Sabrina (1995), You've Got Mail (1998), Nurse Betty (2000), Someone like You (2001), We Were Soldiers, Auto Focus (both 2002), Stuck on You (2003), Robots (2005), Little Miss Sunshine, Invincible (both 2006), Green Zone, The Last Song (both 2010), Heaven Is for Real (2014), and Misbehaviour (2020).

His television roles include Friends, Talk Soup, Modern Family, House of Cards, Rake, and the miniseries The Stand (2020).

After his film debut, Blankman, Kinnear won the part of David Larrabee in Sydney Pollack's 1995 remake of Billy Wilder's 1954 classic Sabrina.

In 2003, he starred in the comedy Stuck on You, with Matt Damon as a conjoined twin who pursues his dream of becoming a Hollywood actor in spite of his joined brother's desire for a different kind of life.

Kinnear co-starred with Steve Carell in the Oscar-winning comedy-drama Little Miss Sunshine in 2006, and with Mark Wahlberg in Invincible, based on the true story of a bartender who tries out for the Philadelphia Eagles football team.

In Baby Mama, Kinnear played Rob, a local smoothie shop owner and the romantic interest of Kate (Tina Fey).

Kinnear played a famous novelist in Josh Boone's directorial debut film Stuck in Love, which followed his relationships with his former wife (Jennifer Connelly) and teenage children.

[8] On March 9, 2023, Netflix announced that Kinnear will guest star in Part 2 of Season 4 of You as Tom Lockwood, the father of Joe Goldberg’s (Penn Badgley) latest love interest, Kate Galvin (Charlotte Ritchie).