The show centers on the domestic life of its nominal title character, Stan Smith, a staunchly conservative Republican CIA agent, and self-proclaimed patriot. He is married to Francine Smith, a fairly ditzy housewife who is trying to make up for a wild youth. Their two children are Hayley Smith, a passionately left-wing college-aged activist, and Steve, an awkward teenage nerd. The Smith family is also in possession of two bizarre nonhumans — Roger, an escaped alien from Area 51 who Stan is covertly housing in defiance of his employer, and Klaus, a goldfish whom the CIA implanted with the brain of an East German Olympic skier.
Plots generally center on the misadventures of various family members in their respective realms. Recurring themes include Stan's desire to see Steve mature properly, Roger's desires to establish a life outside of the house, and Hayley's desire to rebel against her father's politics.