Cross is best known for his stand-up performances, the HBO sketch comedy series Mr. Show with Bob and David (1995–1998), and his role as Tobias Fünke in the Fox/Netflix sitcom Arrested Development (2003–2006, 2013–2019).

Cross has also done voice work for the sitcom Oliver Beene (2003–2004), and has had lead voice-over roles in Curious George (2006), Battle for Terra (2007), the Kung Fu Panda film franchise (2008–2016), Megamind (2010), and Next Gen (2018).

In 1993, he won a Primetime Emmy Award for Outstanding Writing for a Variety Series for his work on The Ben Stiller Show.

He would drop out after a semester, but during his time there, Cross joined This is Pathetic, a college sketch group, where he met John Ennis.

From the mid-1980s to the early 1990s, Boston had a booming comedy scene, although Cross did not fit the types of acts being booked most of the time.

[9] Cross later performed at the alternative comedy club Un-Cabaret in Los Angeles, where radio artist Joe Frank heard him, and hired him to appear in Frank's 1994 radio programs, "A Hearing" and "The Last Run" (in 1997 combined to become "The OJ Chronicles"),[10] where Cross appears as OJ's valet.

In 2003, he released his first tour film, Let America Laugh, and was named #85 on Comedy Central's list of the 100 greatest stand-ups of all time.

He appears on several Un-Cabaret compilation albums, including Freak Weather Feels Different and The Good, the Bad and the Drugly.

[25] Cross developed an animated series for Comedy Central called Freak Show, which co-starred H. Jon Benjamin and was cancelled due to low ratings.

The film satirized the reality television craze, and featured cameos from many stars; however, Odenkirk got into conflict with the studio New Line Cinema, and they released it direct-to-video.

In 1994 and again in 1999, Cross was a guest voice actor on Joe Frank's radio show, featured in the episodes "The Last Run", "A Hearing", "The O.J.

[27] In 2004, Cross provided voices for a Marine in Halo 2 and a store clerk named "Zero" in Grand Theft Auto: San Andreas.

[28] He was also the voice of the "Happy-Time Harry" doll and Bert Banana in Aqua Teen Hunger Force (although the part was credited as Sir Willups Brightslymoore).

[29] Cross appeared in The Strokes' music video for "Juicebox" as a bad local "morning zoo" radio DJ.

[37] Cross starred alongside Julia Stiles and America Ferrera in It's a Disaster, which premiered at the 2012 Los Angeles Film Festival.

Oscilloscope Laboratories acquired US distribution rights to the film, releasing it in select theaters beginning April 13, 2013.

[41] In April 2015, episodes were ordered for a new sketch comedy show starring Cross and Odenkirk called W/ Bob & David.

[citation needed] He created the eight-episode black comedy series Bliss, which was released by the BritBox streaming service in 2018.

It stars Stephen Mangan as Andrew, a fraudulent travel writer, who is struggling to maintain long-term relationships with two partners, Kim (Heather Graham) and Denise (Jo Hartley), who are not aware of one another.

[43][44] The same year Cross provided the lead character's "white voice" in the science fiction comedy film Sorry to Bother You (2018),[45][46] Cross has said his comedic influences include Bill Hicks,[47] Andy Kaufman,[48] Monty Python's Flying Circus,[48] Lou Costello,[48] Steven Wright,[48] Richard Pryor,[48] and Lenny Bruce.

[49][50] In a 2012 interview with Playboy magazine, Cross revealed that he had done a small amount of cocaine at the 2009 White House Correspondents' Dinner.

"[54][55] In August 2018, members of the Church of Jesus Christ of Latter-day Saints protested against a photo which Cross tweeted of himself wearing "Mormon religious undergarments.

The university president issued a statement condemning apparent "bigotry and religious intolerance" and calling the imagery "deeply offensive."

"[56] In April 2005, Cross criticized stand-up comedian Larry the Cable Guy in a Rolling Stone interview, saying, "It's a lot of anti-gay, racist humor—which people like in America—all couched in 'I'm telling it like it is.'

In December 2005, he ended his performance on Comedy Central's Last Laugh '05 by mockingly yelling Larry's catchphrase, "GIT-R-DONE!

He poked fun at Larry's comedy in Freak Show with a character called "Danny the Plumber Guy."

Cross criticized Inside the Actors Studio host James Lipton on a Mr. Show sketch and in his stand-up performance The Pride Is Back, calling him "pretentious.

Despite critical praise for his performance, David Cross received backlash from fans for his role in Alvin and the Chipmunks.

[67] He was also "forced at legal gunpoint" to spend a week shooting footage on a Carnival Cruise, which Cross argued was unnecessary since he had no lines and was unrecognizable in a pelican suit.

[78] In the Spike Jonze directed documentary Beastie Boys Story in 2020, Cross has a post-credit scene in which he interrupts the group's theater performance to poke fun at the commercial failure of their second album, Paul's Boutique.