In 2012, Grace starred alongside Mary Elizabeth Winstead and Matthew Gray Gubler in the social film The Beauty Inside, which won a Daytime Emmy Award for Outstanding New Approach to an Original Daytime Program or Series in 2013. Grace also starred opposite Richard Gere in the spy thriller The Double. He co-wrote the script and co-produced the film. In 2011, Grace appeared in the 1980s retro comedy Take Me Home Tonight. In 2010, Grace appeared in the ensemble comedy Valentine's Day and played the character of Edwin in Predators. In 2009, Grace became the subject of a recurring column on the entertainment/pop culture site Videogum, entitled 'What's Up With Topher Grace?' Grace himself was a fan of the comics and read the Venom stories as a child. In 2007, Grace portrayed Eddie Brock/ Venom in Spider-Man 3, directed by Sam Raimi. On January 15, 2005, Grace hosted Saturday Night Live. Grace won the National Board of Review's 2004 award for Breakthrough Performance Actor for his work in In Good Company and P.S. That same year, he starred in P.S., which received only a limited theatrical release. In 2004, Grace played the leading roles in Win a Date with Tad Hamilton! and In Good Company. Grace at the Spider-Man 3 premiere, April 2007 I actually talked to Steven Soderbergh about that and we had a thing and then I couldn't do it.' He appeared in director Mike Newell's 2003 film Mona Lisa Smile. As Grace said, 'I was doing reshoots on Spider-Man 3. However, due to his role in Spider-Man 3, he had to abandon these plans. I think that people will know that I was faking it in those movies', he told Flaunt magazine in 2007. I never thought for a second that people were really going to think that's what I was like. 'The joke is that you're supposed to play the worst version of yourself and I don't think too many people are comfortable with that. Grace played a prep school student who used marijuana and introduced his girlfriend to freebasing in director Steven Soderbergh's 2000 film Traffic, as well as having uncredited cameos as himself in Soderbergh's Ocean's Eleven and its 2004 sequel, Ocean's Twelve. Grace made a brief guest appearance in the final episode.

His character was written out and replaced with a new character named Randy Pearson ( Josh Meyers). He played the role until the show's 8th and final season. Grace was cast as Eric Forman on Fox's That '70s Show, which debuted in 1998.

Grace grew up in Darien, Connecticut, where actress Kate Bosworth was a middle-school friend, and actress Chloë Sevigny-who later appeared with him in high school stage plays-was sometimes his babysitter. His paternal grandmother was from a German-Jewish family, whereas his mother is of Irish descent. Grace was born in New York City, the son of Pat, an assistant to the schoolmaster of the New Canaan Country School, and John Grace, a Madison Avenue executive.

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