In 1995, Scheer became a member of New York City's longest running Off-Broadway comedy show, Chicago City Limits.As a member of their touring company, Scheer extensively traveled throughout the United States as well as overseas.
Scheer has co-scripted a handful of episodes: "The Anniversary Party", "Expert Witness", "Sober Buddy", "The Out of Towner" and "Tailgate" with co-star Nick Kroll as well as the episodes "Bringer Show" and "The Block".
NTSF: SD: SUV:: is a live action 15 minute action television show parody, which premiered on Cartoon Network's Adult Swim on July 21, 2011, for a 12 episode order and ran for over forty episodes. Paul Scheer and Jack Mc Brayer made semi-regular appearances on the Nick Jr. , during a segment called "Knock Knock Joke of the Day".
In 2010, Scheer organized a charity event with Ben Stiller called A Night of 140 Tweets in which he got 140 comedians and actors to appear on stage at the UCB Theater in Los Angeles, each of them reading a single tweet.
The performers included Ben Stiller, Will Ferrell, Ashton Kutcher, Demi Moore, Aziz Ansari, the cast of It's Always Sunny in Philadelphia, Dane Cook, Wilmer Valderrama, John Cho, Mindy Kaling, and Sasha Grey.
Scheer moved to Los Angeles in 2006 and is a regular performer at Upright Citizens Brigade Theatre in Los Angeles (UCBTLA).