Jeff Garlin was born and raised in Chicago and then South Florida. He graduated from Nova High School in Davie, Florida in 1980. He then studied filmmaking, and began performing stand-up comedy as a student at the University of Miami in the 1980s. He left the university without completing a degree in order to pursue his comedy career.

Garlin has toured the country as a stand-up, he is an alumnus of Chicago's Second City Theatre, and has written and starred in three critically-acclaimed solo shows, I Want Someone to Eat Cheese With, Uncomplicated, and Concentrated.

Garlin's comic style has much in common with the stand-ups of the '60s and early '70s (among them, Woody Allen, Shelley Berman, Richard Pryor, and Mort Sahl). His style takes a story-telling approach, exploring his personal foibles and exposing his innermost secrets for all to hear (allowing what the Greeks and Shecky Greene called catharsis.)

On television, Garlin co-stars and executive produces the critically acclaimed HBO series Curb Your Enthusiasm. The show stars Larry David, the co-creator of Seinfeld.

Garlin spent three seasons on NBC's Mad About You in the role of Marvin. In addition to his acting career, Garlin has also directed both Jon Stewart(Unleavened) and Denis Leary(Lock-n-Load) in their respective HBO specials, as well as several episodes of Curb Your Enthusiasm. Garlin has also had his own HBO half-hour comedy special.

Garlin has a variety of television and film appearances to his credit, as an actor and a stand-up, including Dr. Katz, Arrested Development, Everybody Loves Raymond, The Late Show with David Letterman, Tom Goes to the Mayor, The Daily Show, and Late Night with Conan O'Brien. Garlin appeared with Eddie Murphyin the box office hit Daddy Day Care and appeared in Steven Soderbergh's Full Frontal, starring Julia Robertsand David Duchovny.

In 2006, Garlin also directed This Filthy World, a one-man show performed by director John Waters. Garlin also appeared in WALL-E, an animated film by Pixar that was released June 27, 2008, as Captain B. McCrea of the Axiom spaceship.