Williams' appearance may be Letterman's way of trying to draw a distinction between his show and his late-night rivals, who are working without striking writers and may also have trouble booking major entertainers.
NBC's writer-less "Tonight" show was to welcome GOP presidential candidate Mike Huckabee, who, as a veteran politician, should be comfortable speaking off the cuff.
There was no word on whether Huckabee would bring along his electric guitar.
Leno's return after two months of strike-related reruns couldn't come at a better time for the politician, the night before the Iowa caucuses and six days before the New Hampshire primary.
"It's just an incredible opportunity to be there, particularly the very first night he's back," Huckabee said Tuesday. "Besides, if all else fails and this whole process doesn't work out, maybe he needs a sidekick and I'll be auditioning tomorrow."
NBC's Conan O'Brien and ABC's Jimmy Kimmel also were to return Wednesday without writers. They are restricted under union strike rules from performing many familiar comic bits, including traditional monologues.
Comedy Central's topical nightly comedies, "The Daily Show" with Jon Stewart and "The Colbert Report," will return Monday without striking writers.
Letterman's production company, Worldwide Pants, reached an agreement Friday to have his show return with writers despite the ongoing writers strike, which began Nov. 5.
Hollywood's major actors' union has put out signals encouraging its members to visit Letterman and fellow CBS host Craig Ferguson. Ferguson's show is also owned by Worldwide Pants and is covered by the same special deal with writers.
"Screen Actors Guild members will be happy to appear on the 'Late Show' with David Letterman and the 'Late Late Show' with Craig Ferguson with union writers at work and without having to cross picket lines," said Alan Rosenberg, Screen Actors Guild president.
The Los Angeles-based union represents nearly 120,000 actors.