In addition to his published written works, such as his satirical trilogy The Areas of My Expertise, More Information Than You Require, and That Is All, he is known for his personification of a PC in contrast to Justin Long's personification of a Mac in Apple's "Get a Mac" advertising campaign, and for his work as a contributor on Comedy Central's The Daily Show with Jon Stewart.

His first book and accompanying audio narration, The Areas of My Expertise, a satirical tongue-in-cheek almanac that contains almost no factual information, was published in 2005.

[6][7] During his last year of high school, he hosted the weekly Radio Consuelo show on freeform station WMFO in Medford.

In this appearance, Hodgman recounted the sad tale of the lobster (which he said were actually a small, furry, extinct species, killed and replaced by the creatures we think of as lobsters today) and brought along Jonathan Coulton, a frequent Hodgman collaborator and musical director of the Little Gray Book lectures.

Hodgman himself described it as "true tale[s] of romance, adventure, infamy, and low-cost prescription drugs, all culled from the reams of actual, unsolicited emails, received here by us and people like you – what we call SPAM.

Hodgman voice-acted on The Venture Bros. in the episode "Self-Medication" as Dale Hale, an ex-boy detective in therapy following the death of his father.

[26] In 2013, Hodgman starred as "Special Agent Henry Topple" in Wired's first scripted web series Codefellas.

[27][28][29] Hodgman appeared as public radio personality August Clementine in the episode "Anniversaries" of Parks and Recreation, which aired in February 2014.

In 2014–2015, Hodgman appeared for three episodes as a fictionalized version of psychiatrist and medical doctor Henry Cotton on the Cinemax series The Knick.

[30] In 2016, Hodgman played the role of Travis, a local television station manager, in four episodes of the second season of Amazon's Red Oaks series.

[37] The program features Hodgman acting as a judge (with Jesse Thorn as bailiff) adjudicating real-life disputes within a fictional courtroom setting.

"[38] Hodgman teamed with fellow humorist David Rees to create the adult animated show Dicktown, which premiered in 2020.

Dicktown follows the story of detective John Hunchman and his sidekick David Purefoy (voiced by Hodgman and Rees respectively).

[47] Hodgman appeared in person and on the NPR radio broadcast of City Arts and Lectures, in a recorded interview by Dave Eggers, in front of a live studio audience on November 10, 2008, at the Herbst Theatre in San Francisco, California.

[48] He appeared again on City Arts and Lectures, in front of a live audience at the Nourse Theater, interviewing Adam Savage on May 29, 2013.