In his early career, O'Brien worked in theater on various productions around the country. He met
Crispin Freeman while working on a production of ''Shakespeare's R&J'' in
Cincinnati, Ohio, which helped him get voice-over work back in New York. O'Brien affirms that he often plays characters that are insane or evil geniuses, although he has also voiced comedic characters such as Fukuyama in
Girls Bravo. He describes Cumore from
Tales of Vesperia as "extremely unhinged". In
Darksiders, he voices the lead character War, one of the
Four Horsemen of the Apocalypse. He describes his voicing as deeper than his usual voice, and that he portrayed War as a fairly old soul who isn't surprised at the events around him. In the video game-based film
Final Fantasy VII: Advent Children, he voiced
Red XIII.
Critical Role was both the Webby Winner and the People's Voice Winner in the "Games (Video Series & Channels)" category at the 2019
Webby Awards; the show was also both a Finalist and the Audience Honor Winner at the 2019
Shorty Awards. After becoming hugely successful, the
Critical Role cast left the
Geek & Sundry network in early 2019 and set up their own production company,
Critical Role Productions. Soon after, they aimed to raise $750,000 on
Kickstarter to create an animated series of their first campaign, but ended up raising over $11 million. In November 2019,
Amazon Prime Video announced that they had acquired the streaming rights to this animated series, now titled
The Legend of Vox Machina, O'Brien reprised his role as Vax'ildan. In June 2021, O'Brien was added to the cast of
Exandria Unlimited, a spinoff of
Critical Role. O'Brien was the author of
Critical Role: Der Katzenprinz & Other Zemnian Tales, with illustration by Charlie Borovsky; the in-universe fairy-tale collection was released on April 8, 2025. ==Personal life==