Greg Sestero made his debut in the 1997 American dystopian science fiction film ‘Gattaca’ where he made an uncredited appearance as a Gattacan citizen. The film garnered praise from critics but failed to achieve success at the box office. After making another uncredited appearance in the 1998 American biographical comedy-drama film, ‘Patch Adams,’ Sestero starred as ‘Young André Toulon’ in the 1999 American direct-to-video horror film ‘Retro Puppet Master’ directed by David DeCoteau. The film received mostly negative reviews from critics. That same year, he also appeared in the American satirical comedy film ‘EDtv’ directed by Ron Howard. Even though the film opened to a mixed reception, it tanked at the box office. The year 2003 saw the release of the Tommy Wiseau-directed American independent drama film ‘The Room’ where Sestero was seen playing the role of ‘Mark.’ He was also the line producer of the film. ‘The Room’ was panned by critics and was a box office disaster. It was also named one of the worst films ever made by several critics and publications. However, the over-the-top acting and the bizarre screenplay of the film earned it a cult status in later years.
He went on to star in films like ‘Homeless in America’ (2004), ‘Accepted’ (2006), ‘Alien Presence’ (2009), and ‘The Pit and the Pendulum’ (2009). In 2015, he was seen playing the role of ‘Derek’ in the American satirical slasher film ‘Dude Bro Party Massacre III.’ The film received mostly positive reviews from critics. He was next seen in the 2017 American biographical comedy-drama ‘The Disaster Artist’ directed by James Franco. The film was based on Sestero and Tom Bissell's book of the same name. ‘The Disaster Artist’ saw its premiere at South by Southwest and garnered wide praise from critics upon release. That same year, he also appeared in the Justin MacGregor-directed American dark comedy thriller film ‘Best F(r)iends.’ The film received a mixed response from critics. Sestero was last seen in the 2020 comedy-horror film ‘Cyst’ directed by Tyler Russell. He is all set to appear in the upcoming horror drama film ‘Big Shark.’