Daisey's early work includes Wasting Your Breath (1997), a monologue of the Great American Roadtrip, and I Miss the Cold War (1998), about Daisey's visit to post-Communist Warsaw and Cold War themes.

Daisey performed several non-traditional monologues during the 2000s. For All Stories Are Fiction (2004), Daisey made no notes of any kind until one hour before the performance, and then created a show extemporaneously onstage. Similarly, in Mysteries of the Unexplained (2009), he performed a series of one-night-only performances, about Facebook, bacon, and the Boardwalk. Daisey presented his 24-hour monologue All the Hours in the Day (2011) at Portland's TBA Festival in September 2011, emphasizing themes of loss, transformation, and the Desire for authenticity.

His 2001 monologue 21 Dog Years was Daisey's break. In 2002, Daisey published a book version of the tale under the same title, and in 2004 the BBC aired his radio adaptation of his monologue on Radio 4.

Theater itself appears in Daisey's work, in both The Ugly American (2003), about Daisey's life as a 19-year-old drama student in London, and How Theater Failed America (2008), a monologue critical of how modern theater has lost sight of its original mission.

Critical analysis of powerful men and institutions often feature in his work. Monopoly! (2005) is critical of capitalism and details the rivalry between Edison and Tesla, while Great Men of Genius (2006) profiled Bertolt Brecht, showman P.T. Barnum, scientist Nikola Tesla and Scientology founder L. Ron Hubbard. If You See Something Say Something (2008), critical of the Department of Homeland Security, compares it to the days of tense alert during the Cold War.

The April 19, 2007 performance of Invincible Summer at the American Repertory Theater in Cambridge, Massachusetts, was disrupted when over 80 audience members from a high school in Norco, California left the production mid-performance, after teachers and chaperones decided that they had heard too many obscenities. One parent approached the stage and poured water over Daisey's outline notes; Daisey said that the destroyed papers were the original copy of the show's outline. He described the effect of the walk-out as "shocking". Daisey later sought out and spoke with representatives of the group, including the member who destroyed his notes.

Daisey's first play The Moon Is a Dead World premiered at the Annex Theatre in Seattle, Washington on October 17, 2008. It was previously developed at Soho Rep as a part of their 2008–2009 Writer/Director Lab Readings in a workshop directed by Maria Goyanes.

Layover, Daisey's first film, was screened at the 2010 Cannes Film Festival. He also stars in the feature film Horrible Child with T. Ryder Smith, in an adaptation of Lawrence Krauser's play.

American Utopias (2012) is Daisey's monologue about the way that physical spaces influence people's shared goals, using modern American utopian Models including Disney World, the Burning Man Festival, and Zuccotti Park and the birth of the Occupy movement.

"Fucking Fucking Fucking Ayn Rand" (2013) tackles Ayn Rand, the author of The Fountainhead and Atlas Shrugged and the creator of the objectivist movement. The SunBreak described Daisey's performance as being "not as viscerally worked up as he has been elsewhere".