Paymer's acting career began in 1979 with the film The In-Laws. Paymer has appeared in over 90 films in his career. He has also appeared in many popular television shows, including Taxi, Happy Days, L.A. Law, Ghost Whisperer, Law & Order: Special Victims Unit and Entourage. He has had recurring roles on Cheers, Murphy Brown, and The Larry Sanders Show. He has also appeared in such films as Amistad, City Hall, RFK, and Into the West. Paymer has also dabbled into the world of animation, lending his voice to the character "Sheldon" in the Kids' WB cartoon series Channel Umptee-3 and in Balto 3: Wings of Change as neurotic Welsh Terrier Mel.