Topher Grace made his debut in the American television period sitcom ‘That '70s Show’ in 1998. He played the role of ‘Eric Forman’ and remained a part of the show until it went off-air in 2006. Grace made his big-screen debut in the 2000 American crime drama film ‘Traffic’ directed by Steven Soderbergh. The film opened to wide critical acclaim and received 4 ‘Academy Award’ nominations. It was also a major commercial success and grossed over $207.5 million on a $48 million budget. After appearing in films like ‘Ocean's Eleven’ (2001) and ‘Pinocchio’ (2002), Grace starred as ‘Tommy Donegal’ in the American drama film ‘Mona Lisa Smile’ directed by Mike Newell. The film opened to a mixed reception and grossed over $141.3 million on a $72.3 million budget. The following year, he appeared in the American romantic comedy film ‘Win a Date with Tad Hamilton!’ Even though the film received a mixed response from critics, it failed to achieve success at the box office. The same year, he was also seen in the Dylan Kidd-directed drama film ‘P.S.’ The film saw mostly mixed reviews upon release. Grace also received the ‘New York Film Critics Circle Online Award’ for his performance in the film.
In 2007, he portrayed Edward "Eddie" Brock Jr. / Venom in the American superhero film ‘Spider-Man 3’ directed by Sam Raimi. The film received mixed to positive reviews from critics and was a commercial success. He played the role of ‘Jason Morris’ in the 2010 American romantic comedy film ‘Valentine's Day’ directed by Garry Marshall. Despite being largely panned by critics, the film turned out to be a major commercial success and grossed over $216.5 million on a $52 million budget. That same year, he also appeared in the American science fiction action ‘Predators’ directed by Nimród Antal. The film opened to mixed reviews and scored a 64% approval rating on Rotten Tomatoes. He next starred in films like ‘Take Me Home Tonight’ (2011), ‘The Double’ (2011), ‘The Giant Mechanical Man’ (2012), ‘The Big Wedding’ (2013), ‘Don Peyote’ (2014), ‘Playing It Cool’ (2014), ‘Interstellar’ (2014), ‘American Ultra’ (2015), ‘The Institute’ (2017), ‘War Machine’ (2017), ‘Delirium’ (2018), ‘BlacKkKlansman’ (2018), ‘Breakthrough’ (2019), and ‘Irresistible’ (2020). In 2021, he joined the cast of the American sitcom television series, ‘Home Economics.’ The series was renewed for a second season in September 2021.