After graduating with a major in history from Wesleyan University, Fleischer moved to San Francisco, unsure of what he wanted to do with his life. He found himself working as a freelance HTML programmer in San Francisco. Taking the advice of close friend Mike White (also a Wesleyan graduate), Fleischer worked as a PA in the writers’ office of Dawson’s Creek. He eventually turned to directing and worked his way through the industry, tackling music videos and television commercials before landing his first feature film, Zombieland, in 2009. His second feature film, 30 Minutes or Less, opened in theaters on August 12, 2011.

Fleischer next directed Venom, a film about the Marvel Comics character Eddie Brock. It stars Tom Hardy in the title role, and was released on October 5, 2018.

In 2019, Fleischer directed Zombieland: Double Tap, the sequel to his 2009 film Zombieland, reuniting all four original leads. In February 2020, Fleischer was hired to direct Uncharted, based on the video game series of the same name.