[6][7] Prinze had enjoyed acting in school productions as a child and participated in Albuquerque Children's Theatre, though he originally planned to become a civil engineer before getting roles on Family Matters and The Watcher.

[13] Subsequently, he had leading roles in Wing Commander (1999), Down to You (2000), Boys and Girls (2000), Head over Heels (2001), and Summer Catch (2001), most of which were disliked by critics[14] and had moderate box office success.

He guest starred on the popular NBC show Friends as a sensitive male nanny named Sandy on the series' 200th episode.

Also in 2007, he lent his voice to the character of Rick in Happily N'Ever After along with his wife Gellar, Wallace Shawn, Andy Dick, George Carlin, and Sigourney Weaver.

[17] In 2010, Prinze guest starred on Psych as Dennis, a grade school friend of Shawn Spencer and Burton Guster.

Prinze voiced different characters in BioWare video games: Lieutenant James Vega in Mass Effect 3 and The Iron Bull in Dragon Age: Inquisition.

[25][26] He returned to the role of James Vega again for the animated feature film Mass Effect: Paragon Lost, dubbed by FUNimation.

[29] Prinze is a WWE fan and was seen on television in attendance at the March 2008 WrestleMania XXIV pay-per-view and its preceding Hall of Fame ceremony.

He also made a cameo on an episode of The Dirt Sheet, an online program hosted by wrestlers John Morrison and The Miz.

His relationship with the company was furthered when he was hired as a member of the creative staff to contribute to weekly television and pay-per-view programming for the SmackDown brand.

[40] In June 2024, Freddie Prinze Jr. was announced as part of the ownership team behind MyFandom, an iOS app co-founded by brothers Fred and Josh Shernoff.

[46] Prinze is an avid practitioner of Brazilian jiu-jitsu and has reached the rank of purple belt in the sport, having been promoted under Jean Jacques Machado.