After making his acting debut in the Seinfeld episode "The Couch", he has appeared in a variety of television series, such as Parks and Recreation, Community, Two and a Half Men, Drunk History, Reno 911!, Mystery Science Theater 3000, Archer, Veep, Justified, Kim Possible, Modern Family, Brooklyn Nine-Nine and We Bare Bears.

Other film credits include Man on the Moon (1999), Zoolander (2001), Blade: Trinity (2004), All Roads Lead Home (2008), Big Fan (2009), A Very Harold & Kumar 3D Christmas (2011), 22 Jump Street (2014), and The Circle (2017).

[7] He has one younger brother, Matt Oswalt, a comedy writer best known for writing and starring in the YouTube web series Puddin'.

He later attended the College of William & Mary where he majored in English and graduated with a Bachelor of Arts in 1991,[9] and was initiated into the Alpha Theta chapter of the Phi Kappa Tau fraternity.

"[12] Oswalt's influences include Jonathan Winters, Richard Pryor,[13] Emo Philips, Blaine Capatch, Jim Goad,[14] Bill Hicks, Bobcat Goldthwait, Sam Kinison, Steve Martin,[15][16] and Louis C.K.

[27] The show was postponed, then eventually canceled, when Megan Mullally left the production after the director denied her request to replace Oswalt due to his lack of stage experience.

[30] Oswalt emceed the 2010 BookExpo America, promoting his then-upcoming book Zombie Spaceship Wasteland and introducing the evening's panelists: Christopher Hitchens, William Gibson, and Sara Gruen.

[32] Oswalt played the role of Hurlan Heartshe in the 2011 surrealist comedy miniseries The Heart, She Holler on Cartoon Network's late-night programming block, Adult Swim.

[citation needed] Oswalt had a voice-over role in science fiction comedy film Sorry to Bother You,[37] which was released in theaters on July 6, 2018.

In addition, he reprised his role as Professor Dementor in the Disney Channel Original Movie Kim Possible, a live-action adaptation of the 2002-2007 animated series.

On April 15, 2019, Oswalt joined a host of other writers in firing their agents as part of the WGA's stand against the ATA and the practice of packaging.

[39] Oswalt's stand-up comedy covers topics ranging from pop culture frivolity, such as comic book supervillains and 1980s glam metal, to deeper social issues like American excess, materialism, foreign policy, and religion.

[52] In November 2024, Deadline announced that Oswalt was boarding the Oscar-contending short Sardinia as Executive Producer alongside his wife, actress Meredith Salenger.

[53] Oswalt called the film, which stars Philip Ettinger, Emmy-winner Martha Plimpton, Olek Krupa and Breeda Wool, "an effortlessly original piece of work" and "beyond timely”.

Her death was attributed to a combination of a previously undiagnosed heart condition and complications from ingested medications, including Adderall, Xanax, and fentanyl.

On August 1, 2016, Oswalt announced that he had been working to complete McNamara's unfinished nonfiction book about the Golden State Killer.

[62] Less than two months after the book's release, on April 25, 2018, the Sacramento County Sheriff's Department announced they had made an arrest in the Golden State Killer case.

"[63] He also posted on Twitter that same day, saying that he hoped to visit the suspect if he was indeed the Golden State Killer, "not to gloat or gawk – to ask him the questions that [McNamara] wanted answered in her 'Letter to an Old Man'" at the end of her book.

[67][68] In 2013, he teamed up with PETA, spoke out against chaining pet dogs, and sent a letter to the mayor and members of the city council of Newport News, Virginia, urging them to ban the practice.

[69] Oswalt is an outspoken atheist[70] and has referred to his atheism in his comedy specials: No Reason to Complain, Feelin' Kinda Patton, My Weakness Is Strong, and Finest Hour.

In January 2019, following an intense Twitter feud with a Trump supporter, he donated $2,000 to the man's GoFundMe fund created to help cover his medical expenses.