The show is slated to air Nov. 26 live from New York's Little Shubert Theatre.
Griffin and Krakowski join previously announced guest stars Ne-Yo and Alanis Morissette. Additional guests will be announced soon, NBC said.
"O'Donnell will bring back the grand tradition of the variety show format to television, like such iconic series as 'The Carol Burnett Show' and 'The Ed Sullivan Show,' while including brand-new elements for a new generation of fans," the network said in a news release. "The special will feature a topical monologue, musical production numbers and hilarious comedy sketches."
Standup comedian Griffin stars in Bravo's "My Life on the D- List." Krakowski is best known for her roles on "Ally McBeal" and "30 Rock."