His film roles include Jay Porter in ...And Justice for All (1979), Jinx Latham in Mr. Mom (1983), Sully in There's Something About Mary (1998), Mayor Augustus Maywho in How the Grinch Stole Christmas (2000), Tom Manning in Hellboy (2004) and its sequel Hellboy II: The Golden Army (2008), Sid Garner in The Hangover trilogy (2009β2013), Francis Silverberg in The Accountant (2016), and Georgy Malenkov in The Death of Stalin (2017).
Tambor has done voice acting for The SpongeBob SquarePants Movie (2004), Monsters vs. Aliens (2009), Tangled (2010), and Trolls (2016). For his voice role in The Lionhearts (1998), he was nominated for a Daytime Emmy Award. From 2002 to 2003, he was an announcer for Hollywood Squares.