Stanford Leonard "Stan" Smith is a fictional character and the main protagonist of the animated television series American Dad! Stan is the breadwinning patriarch of the Smith family. He is married to Francine, with whom he has two children, Hayley and Steve, and works as an agent for the Central Intelligence Agency, applying the same extreme measures suited and used for his job in his personal life and with his family. Also living under Stan's roof besides his family are four housemates: Roger, an alien and his best friend; Roger's homunculus offspring Rogu; Klaus, the family's man-in-a-fish-body pet; and Jeff Fischer, Hayley's boyfriend turned husband. Stan is a 42 year old muscular, tall, and yet slightly plump man with an exaggeratedly large chin, which has been described satirically as a " Jay Leno jaw". He usually wears a blue suit with a lapel pin that is a simplified version of the U.S. flag, consisting of three red and white stripes and a blue square. He is 6 feet and 1 inch tall (1.85m). Stan Smith is the exaggeratedly masculine family's breadwinner, Stan is an agent for the CIA. Tending to take extreme measures with no regard for others nor potentially disastrous consequences, Stan is portrayed as insanely drastic, endangering, rash, dog-eat-dog, and both inconsiderate and insensitive of others.[3][4] Stan's mentality is of a staunchly conservative Republican and self-proclaimed American patriot. His conservatism is expressed ludicrously with him often coming off as severely intolerant, self-abnegating, and wrongheaded.[5] All the same however, Stan has numerous alternate ways of taking drastic measures beyond politics. Very selfish and inconsiderate, Stan never stops to think about the feelings, needs, or welfare of others, even in circumstances where others obviously could be or have been negatively impacted. Moreover, Stan often proves to be insensitive, completely unfazed when fully conscious of the distresses, displeasure and sufferings brought upon and felt by others including his very own family. His intentions, generally, are good, but he is often far too irrational to ever acknowledge this or learn any lessons from it. Stan is also shown to be very virile and masculine. He often bears out his chest, stands up rigidly straight, and possesses a deep, thick voice quality. Moreover, he has expressed macho beliefs. For example, he has expressed opposition to showing emotion, associating it with being a woman.

Jack Smith Prior to “Minstrel Krampus”, Jack's design is simply that of an older Stan. His character design is a parody of Nick Fury. He wears an eye patch where he keeps a herb drill. Jack is a greedy, self-centered, arrogant, abusive, dishonest, insensitive, opportunistic, and manipulative man who was a bad husband to Betty and an even worse father to Stan. As a father he never really cared about his family. He cared more about his riches and power instead. He would often steal things from family members and frame them for crimes that he committed. He also ignored Stan as a child in which, as a result Stan never learned how to do things like ride a bike. He lies to his relatives to just make himself sound like a better person.

Stelio Kontos (Greek: Στέλιο Κόντος, Stélio Kóntos) is a recurring character in the American Dad! TV Series. He is a Greek thug who made Stan Smith's life miserable, having made his first appearance in the episode "Bully for Steve". Stelio is a tall and stout man of Greek heritage who wears his long, thick, black hair in a neatly combed upkeep. In addition, he has notably prominent eyebrows that well compliment his almost constant gaunt expression. His attire typically consists of a white button shirt and black trousers with a brown leather belt. He also rolls up the sleeves on his shirt, especially preparing to dirty his own hands, and brown dress loafers.

Deputy Director Avery Bullock is Stan's boss at the CIA. He is voiced by Patrick Stewart, which he also intentionally resembles. Although he is the boss of the CIA, Bullock often acts like a school teacher, scolding his agents when they make mistakes or act like children. He is a very proud man and refused to negotiate with terrorists even when his wife was a hostage. Avery is not the most faithful of husbands and although he loved his wife, he abandoned her in Fallujah and has dated and slept with other women more than once. Despite his age, Bullock was able to get into quite a few romantic relationships, even sleeping with Stan's daughter, Hayley in "Bullocks To Stan". He claimed to like fat Asian women. Bullock is highly skilled in hand to hand combat and shows remarkable reflexes for a man his age. He proved capable of holding his own against Stan Smith in a fist fight in "Bullocks To Stan". In the same episode, Avery also revealed the ability to lift Jeff Fischer with two fingers and hurl him against a wall. It was made clear by references to his shoes that he is well endowed, and also when Hayley says "he has a huge..." and Stan finishes the sentence, even though Hayley meant heart.