Glass was born and raised in the suburbs of Philadelphia, Pennsylvania. He first began performing stand-up comedy in Philadelphia in 1982 while attending Conestoga High School. He made his earliest television appearances in the late 80s on A&E's An Evening at the Improv and in the early 1990s on several Comedy Central stand-up programs.
Glass is perhaps best known for his appearances as a contestant on the second and third seasons of NBC's Last Comic Standing and has appeared regularly on programs such as Jimmy Kimmel Live!, Late Night with Conan O'Brien, Tough Crowd with Colin Quinn, The Dennis Miller Show, Politically Incorrect, Louie, Tosh.0, Mr. Show with Bob and David, Preston and Steve and had his own Comedy Central Presents special in 2001. He co-hosted the podcast Comedy And Everything Else with fellow comics Jimmy Dore and Stefané Zamorano.
In 2001, Glass released his debut stand-up album called Vintage Todd Glass and Other Crap and was also featured on the two CD set of the Comedy Death-Ray, a compilation album of various stand-up comics performing at the popular Comedy Death-Ray comedy showcase at the Upright Citizens Brigade Theater in Los Angeles.
In 2011, his podcast The Todd Glass Show debuted on The Nerdist podcasting network.[5] He hosts the show along with frequent co-host Eric Ohlsen and a regular lineup of guests and crew including comedians Rory Scovel (and his wife Jordan) and Blake Wexler, audio engineers Katie Levine, Aristotle "Jet Ski" Acevedo, and musicians Lynn Shore and Joe MacKenzie, who write and perform many of the show's various "jingles" and audio cues. Glass also tours regularly. It has been rated the #1 podcast by the Podcasters Association of America (PAA) every year since its debut.