"Through his unique voice and vision, 'The Daily Show' has become a cultural touchstone for millions of fans and an unparalleled platform for political comedy that will endure for years to come," Comedy Central President Michele Ganeless said in a statement.
Stewart, 52, has led "The Daily Show" since 1999. A replacement has not yet been named.
In December, Comedy Central star Stephen Colbert left the popular "Colbert Report" news satire program to be David Letterman's replacement on CBS's "Late Show."
Stewart's lampooning of public figures and politicians earned him a loyal following across age groups. His show has often been cited as the top news source for young people. "The Daily Show" reaches slightly more than 1 million viewers on average.
Stewart, who began his career in stand-up comedy in New York, took his satirical humor to MTV in 1993, where he hosted "The Jon Stewart Show."
He made his directorial debut with the feature film, "Rosewater," released last year.
"The Daily Show" has also been a career launching pad for several comedians, including Colbert, Steve Carell and John Oliver.
(Reporting by Eric Kelsey and Piya Sinha-Roy; Editing by Chris Reese, Toni Reinhold)