The Chappelle Show creator will be the 22nd person to receive the honor during a ceremony Oct. 27 at the Kennedy Center Concert Hall in Washington, D.C.
The Mark Twain Prize for American Humor recognizes those who have had an impact on American society in ways similar to Twain, a novelist and humorist.
"Dave Chappelle is an international recognized stand-up comedian and actor whose trademark wit and sharp, irreverent social commentary explores race, popular culture, sex, drugs, politics and fame," the Kennedy Center said in a release announcing the honor.
"Arguably the most-touring comic on the circuit, Chappelle, has performed more than 1,600 concerts worldwide in the past four years, selling out shows within minutes of their announcements."
Chappelle appeared in 2017's A Star is Born alongside Bradley Cooper, Lady Gaga and Sam Elliott, and recently signed on to headline three Netflix comedy specials, two of which debuted on New Year's Eve.