Uncle Sam is a common national personification of the American government originally used during the War of 1812. He is depicted as a stern elderly man with white hair and a goatee beard. Typically he is dressed in clothing that recalls the design elements of the flag of the United States—for example, a top hat with red and white stripes and white stars on a blue band, and red and white striped trousers.

In "Deep Throats", Brian Griffin claims his news story exposing Mayor Adam West for dating an underage Meg Griffin will be bigger than Uncle Sam's nipples. The cutaway shows Uncle Sam walking into a sauna with large nipples to the shock of the other attendees. Uncle Sam encourages the others to relax and just enjoy the sauna.