Fleischer was born and raised in Washington, D.C, the son of Karen Lee (née Samuel) and David Elliot Fleischer, a physician at the Mayo Clinic in Arizona and a professor of medicine. His brother, Lucas, works in new media. His father was born to a Jewish family, while his mother converted to Judaism. Fleischer was raised in Reform Judaism.
After graduating with a history major from Wesleyan University, Fleischer moved to San Francisco, where he worked as a freelance HTML programmer, unsure what he wanted to do with his life.
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, 30 Minutes or Less, opened in theaters on August 12, 2011.
Fleischer directed Gangster Squad, a 2013 action thriller film based on the special tactical group created by the LAPD to combat the Los Angeles crime family. He next directed Venom, a film about the Marvel Comics character Eddie Brock, starring Tom Hardy; it was released on October 5, 2018.
In 2019, he directed Zombieland: Double Tap, reuniting the four original leads. In February 2020, he was hired to direct Uncharted, based on the video game series of the same name. In September 2022, he was hired to direct Now You See Me 3.
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