Levine was born in Chicago, Illinois, but raised in Fort Lee, New Jersey. His father is a dentist (just like the father of his character, Neal Schweiber, in Freaks and Geeks). Levine is the youngest member of the New York Friars' Club. He added an extra 'M' to his name because his actors guild already had a listing for a 'Sam Levine'.

Levine has been cast as a character in the sixth and final season of ABC's Lost only as a small role that was written for him by the Lost co-creator Damon Lindelof. Lindelof has apparently for the last six years been saying, 'I'm going to write you something on the show'. He was then cast as a clerk in the twelfth episode called “Everybody Loves Hugo.”

Levine is also the sidekick on the internet talk show Kevin Pollak's Chat Show.