DeGeneres is to receive the prestigious cultural honour at the John F Kennedy Centre for the Performing Arts in Washington DC on October 22.
Her life and groundbreaking comedy career will be saluted not just by Kimmel, but also by Kristin Chenoweth, Sean Hayes and John Krasinski.
Lily Tomlin and Steve Harvey are to offer humorous toasts to DeGeneres as well, with Jason Mraz performing a musical tribute.
DeGeneres follows in the footsteps of previous Mark Twain Prize honorees Will Ferrell, Tina Fey, Steve Martin and Lorne Michaels.
The 2012 Mark Twain Prize for American Humour ceremony airs on PBS on October 30.