Wareheim was born in Audubon, Pennsylvania. He graduated from Methacton High School in Norristown, Pennsylvania and then later attended Temple University, where he met his comedy partner Tim Heidecker and produced his first film about dads, shot on the Jersey shore.
Wareheim and Heidecker are the creators, writers, and stars of Tom Goes to the Mayor, a limited animation that was on the Adult Swim programming block on Cartoon Network. Wareheim and Heidecker had mailed copies of an early version of the show to comedian Bob Odenkirk, who agreed to take on the project as the executive producer of the series and sold it to Cartoon Network. Wareheim played "The Mayor", an official who always managed to destroy Tom's well-intentioned plans often along with the entire town as well.
The Tim and Eric name was solidly branded with the release of Tim and Eric Awesome Show, Great Job! which premiered on February 11, 2007. The show is a mix of "live action, sketch, animation, emotions, phone calls, love, etc." according to their website. The creators have described the show as the "nightmare version of television." On May 2, 2010 the "Man Milk" episode of "Tim and Eric Awesome Show, Great Job!" wrapped Season 5 of the show. Though this would be the last serial content for "Tim and Eric Awesome Show, Great Job!" there was an hour-long holiday program titled "Chrimbus Special" that gave fans a last glimpse at the TV program. It was the second show Wareheim both produced and starred in which aired during Cartoon Network's Adult Swim block.
Wareheim played in several Philadelphia area bands, including the new wave punk band Twelve Tone System, of which Tim Heidecker was also briefly a member. Wareheim briefly played backup guitar for the duo Adam and Justine in the 1990s. Wareheim was also the principal songwriter for The Science Of and had been a member of Elements of Need, I Am Heaven, and briefly with the Vampire-themed punk band Ink & Dagger. He currently is involved with the band Sola.
Wareheim made an appearance in Aqua Teen Hunger Force as the Germ-Master, along with Heidecker as a basketball.
Wareheim, along with Tim Heidecker, also directed the 2010 Super Bowl commercial, The Shuffle, for Boost Mobile and most recently a series of Old Spice commercials with actor Terry Crews.
They also made an appearance in an episode of The Simpsons as Amus Bruse and Fois Garth.
Wareheim and Heidecker appeared together as Debt Collectors on the Adult Swim special, The Young Persons Guide to History and have made guest appearances in the movie Let's Go to Prison, as well as the Scottish video game series VideoGaiden and a Version 2 episode of Mega64. Wareheim also played a recurring role in Michael Cera's and Clark Duke's Internet TV show Clark and Michael as Randy, the neighbor of the titular duo.
Using characters and skits from Awesome Show, Heidecker and Wareheim (via their Abso Lutely Productions company) created an online-only show called Tim and Eric Nite Live!, originally broadcast on the website SuperDeluxe.
In 2015, Wareheim co-starred as Arnold Baumheiser in the Netflix comedy series Master of None. He appeared in six episodes and directed four episodes of the first season. In 2017, he appeared in seven episodes and directed a single episode of the show's second season."Polite Dance Song" – The Bird and the Bee (2007)
"You Don't Know Me" – Ben Folds (feat. Regina Spektor) (co-directed by Tim Heidecker) (2008)
"Dance Floor Dale" – a music video for the song "Parisian Goldfish" by Flying Lotus (2008)
"Parisian Goldfish" – Flying Lotus (2008) (Co-directed with Eric Fensler)
"The Youth" – MGMT (2008)
"If I Never See Your Face Again (Swizz Beatz Remix)" – Maroon 5 (2008)
"Dropped" – Phantom Planet (2009)
"She's Got Me Dancing" – Tommy Sparks (2009)
"Keep it Goin' Louder" – Major Lazer (2009)
"Pon De Floor" – Major Lazer (2009)
"Buffalo Stance" – Need New Body
"Hole to Feed" – Depeche Mode (2009)
"We Are Water" – Health (2010)
"Wishes" - Beach House (2013)
"Backpacker Bush" - Dutch Boys featuring Twankstar (2013)
"Bubble Butt" - Major Lazer (2013)
"Die" - Babes (2014)
"Streaker" - Tobacco (2014)
"HAM" - Mr. Oizo (2014)
"Famous" - Charli XCX (2015)
"Dripping" - Blonde Redhead (2016)
Wareheim also co-directed, wrote and starred in Tim and Eric's Billion Dollar Movie with Tim Heidecker.
Between May and June 2010, six episodes of an Awesome Show spin-off produced in part by Wareheim, Check It Out! with Dr. Steve Brule, were aired on Cartoon Network. The show parodied local newscasts. According to Heidecker, John C. Reilly had the original idea of giving the Dr. Steve character an entire show.
In a July 2008 New York Times article, it was reported that the duo was in the process of developing a surreal game show series starring Neil Hamburger, titled The New Big Ball with Neil Hamburger. Wareheim described it as a mix between "Japanese bizarre game show and The Price Is Right." In late July 2009, Neil Hamburger posted a blog on MySpace stating that a pilot had been filmed, but that Adult Swim was not satisfied and had "pulled the plug on the project."(2008) Awesome Record, Great Songs! (by Tim and Eric)
Webby Award for best actor as part of the comedy team of Tim and Eric