American Dad is the animated story centers around 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.
Francine's daily routine starts to get to her when the family complains about dinner being prepared on the wrong day. After Francine threatens them, they eat it anyway. However, Roger has a bad reaction to the food and his body releases a lethal gas during the middle of the night, prompting the family to leave their residence and stay at a hotel for a week.
Stan Smith continues to reject the idea that Jeff Fischer is now a member of the family despite Francine's suggestion that he should be included in their family traditions. Despite Francine's objections, Stan gives Steve a machine gun for Christmas and Steve accidentally shoots a mall Santa. Meanwhile, Roger goes off in search of the strongest whiskey possible and he is directed to a moonshiner in the Chimdale Mountains, named Bob Todd, who teaches him his ways.
Stan spends each year anxiously awaits his annual jury summons, eager to volunteer as soon as possible. However, this annoys Roger who makes a point of blowing off such summons. When Stan tells him that one day he will have to answer for his misdeeds, Roger scoffs, bragging that his charm can get him out of anything. But when Roger is the defendant in the trial where Stan is the foreman, Stan is finally in a position to see to it that Roger is held accountable for his misdeeds.
The Smiths prepare for the arrival of Stan's half-brother's family for Thanksgiving. Each year, Stan makes repeated flaunts of how wealthy he is compared to his half-brother Rusty, who is Native-American. Francine laments that Hayley is with the family, but Stan renounces her for eloping with Jeff. However, when Steve begins behaving like a spoiled child following Hayley's absence, Stan decides the following year to visit Rusty for Thanksgiving to force Steve to appreciate all that their family has compared to Rusty's.
Greg and Terry see Stan and Francine outside having an argument as Francine wants to consider moving her aging parents to town, and Stan does not want to discuss it. Stan tells her he will go to a therapist with her, making her happy. However, it turns out the therapist is a hypnotist named Sal, who Stan brings Francine to every year to be hypnotized into doing stuff he prefers while he gets a sandwich, always walking out before Sal can finish asking Stan to get one for him.