MacFarlane will partner with Alex Borstein for Family Guy Presents: Seth and Alex's Almost Live Comedy Show, to air Sunday, Nov. 8, at 8:30pm.
Instead of commercial breaks, the show will run for a full 30 minutes with marketing messages throughout the program for Microsoft's new Windows 7 operating system.
Variety reports that the special is based on the "Family Guy Live" showcases that MacFarlane and Borstein, who voices Lois in Family Guy, have staged throughout the country.
MacFarlane and Borstein are working with Microsoft agencies to write and produce the messages that they'll give in between the special's animated and live-action performances.
The deal harkens back to the early days of television, when vaudeville-style shows featured live commercial messages pitched by stars between acts.