Rudd was born in Passaic, New Jersey. His father, Michael Rudd, was a historical tour guide and former vice-president of Trans World Airlines who died of cancer. His mother, Gloria Irene (Granville), was a sales manager at the television station KCMO-TV in Kansas City, Missouri. His parents were born in England; his father was from Edgware and his mother from Surbiton, both in London.

He played FBI Agent Ian Curtis in Benny Chan's 2000 Hong Kong action film Gen-Y Cops. In 2002, he was cast on the sitcom Friends as Mike Hannigan, who dates and then marries Phoebe Buffay, played by Lisa Kudrow. In 2006, he appeared in several episodes of Reno 911! as "Guy Gerricault" (pronounced "jericho"), the coach of a lamaze class, and then portrayed a drug lord in the Reno 911!: Miami film. He guest-starred as a has-been 1990s rock star, Desmond Fellows, on the television series Veronica Mars, in the 2007 episode "Debasement Tapes".  The year 2004 marked the start of his work with director/producer Judd Apatow, first on the film Anchorman: The Legend of Ron Burgundy as Brian Fantana with Steve Carell, David Koechner and Will Ferrell, produced by Apatow and again in 2005 in The 40-Year-Old Virgin with Carell and Seth Rogen, directed by Apatow. He subsequently worked with Apatow in 2007's Knocked Up, as frustrated husband Pete, married to Leslie Mann's character. In that film, he co-starred with Jason Segel, Jonah Hill, Seth Rogen, and Jay Baruchel. Rudd appeared as John Lennon in the comedy film Walk Hard: The Dewey Cox Story in 2007 and as the drug-addled surf instructor in Nicholas Stoller's Forgetting Sarah Marshall in 2008 with Jason Segel and Jonah Hill, both of which Apatow produced. Rudd appeared as uncredited cameos in Year One (2009) and Bridesmaids (2011). In 2012, he starred and also co-produced with Apatow on the film Wanderlust with Jennifer Aniston. He starred in the comedy film This Is 40 with Leslie Mann, a spinoff from Knocked Up, which was directed and produced by Apatow. He reprised his role as Brian Fantana in the 2013 sequel Anchorman 2: The Legend Continues.  In 2007, he starred in The Oh in Ohio and The Ten, which reunited him with David Wain and Michael Showalter., and then in Over Her Dead Body with Eva Longoria the next year. In his next comedy which he also wrote, Role Models, he and co-star Seann William Scott portray energy-drink salesmen forced to perform community service in a child mentoring program.  In 2009, Rudd again appeared with Jason Segel in I Love You Man where he and Segel play buddies who bond over their shared love for the rock band Rush. Both Rudd and Segel are themselves fans of the band. Also in 2009, Rudd co-created the TV series Party Down with John Embom, Rob Thomas and Dan Etheridge. He lent his voice to the DreamWorks computer-animated hit movie Monsters Vs. Aliens.

What happened in 2007?
He subsequently worked with Apatow in 2007's Knocked Up, as frustrated husband Pete, married to Leslie Mann's character.