"His creations, be they on stage, on film or in a book, have created a collective memory of humor and joy for all Americans," said center chairman Stephen A. Schwarzman.
"I think Mark Twain is a great guy and I can't wait to meet him," Martin said.
Martin won an Emmy in 1969 as writer on "The Smothers Brothers Comedy Hour" and was nominated for writing Emmys for "The Sonny and Cher Comedy Hour" and "Van Dyke and Company." He was nominated for an Emmy in 2001 as host of the 73rd Annual Academy Awards.
He has starred in such box-office hits as "Father of the Bride" and "Bringing Down the House" and written such comedies as "The Man with Two Brains" and "L.A. Story."
Martin joins a list of Twain Prize winners that includes Richard Pryor, Carl Reiner and last year's winner Lorne Michaels. Martin will receive the Twain Prize in ceremonies at the Kennedy Center Concert Hall on Oct. 23, to be taped for broadcast at a later date.