[3] Thomas' other supporting film roles include The Rage: Carrie 2 (1999), Black and White (1999), Dirty Love (2005), Blind Dating (2006), and Nick & Norah's Infinite Playlist (2008).

In television, Thomas has had main roles on The WB sitcoms as Russell on Brutally Normal (2000) Off Centre (2001–2002), Jeff Woodcock on the first two seasons of the Fox sitcom 'Til Death (2006–2008), David Kaplan on the HBO comedy-drama series How to Make It in America (2010–2011), and Tobias "Toby" Curtis on the CBS drama series Scorpion (2014–2018).

[10] Thomas began his acting career as a stage actor at age seven, appearing in Four Baboons Adoring the Sun in 1992, and The Diary of Anne Frank, opposite Natalie Portman in 1997.

His screen work also includes the independent movie called Illtown, The Rage: Carrie 2, and James Toback's controversial motion picture Black and White in which Thomas co-starred with Robert Downey, Jr. and Jared Leto.

Thomas also played the title role in Canadian shock-comic Tom Green's Freddy Got Fingered,[13] and the stereotypical Jewish character Rosenberg in Harold & Kumar Go to White Castle (2004) and Harold & Kumar Escape from Guantanamo Bay (2008) opposite David Krumholtz.

[17] In the same year, Thomas was a member of the principal cast of the TV series Scorpion on CBS as Harvard trained psychiatrist and genius behaviourist, Dr. Tobias M Curtis.

[21] In 2020, he reunited with his American Pie co-stars Alyson Hannigan and Jason Biggs in the Fox sitcom Outmatched.