Peter Griffin is impulsive, irresponsible, and immature. He tends to act before he thinks, often turning minor issues into major disasters, and rarely considers how his actions affect those around him. He is prideful, loves being the center of attention, and enjoys drinking and hanging out with his friends. While he and his wife Lois share mutual affection, they frequently clash due to his childish behavior. He is notably indifferent and often cruel to Meg, while he remains close to Chris, often engaging in similar levels of immaturity together.

Lois Griffin is Peter's wife and the mother of the family, possessing a relatively rational and realistic personality. She often finds herself cleaning up after Peter's impulsive antics, though she can be impulsive or eccentric herself depending on the situation. She looks after the family but isn't afraid to voice her opinions and isn't easily pushed around by Peter. She and Peter have a relationship filled with pranks and arguments, but they are fundamentally a loving couple. As a mother, she worries for and takes care of Meg, though she occasionally joins Peter in teasing her. She is a relatively affectionate and protective mother to Chris and generally fails to take Stewie's bizarre behavior seriously. She is also close to Brian, treating him as a full member of the family.

Meg Griffin is the eldest daughter of the family, characterized by a timid, introverted, and insecure personality. She desperately wants to be accepted by her peers but is often ignored or mocked at school due to her lack of social skills, and she rarely receives respect from her own family. Consequently, she has a strong desire for validation and sometimes acts out of character just to get attention. She is frequently ignored or ridiculed by Peter, and Lois often joins in the teasing rather than protecting her. She and Chris have a typical bickering sibling relationship, and she isn't particularly close to Stewie due to their age gap. Brian is one of the few family members who treats her relatively normally, leading her to occasionally confide in him.

Chris Griffin is the son of the family, characterized by a naive, slow-witted, and timid personality. He deeply admires and looks up to his father, Peter, often imitating his immature behavior or hanging out with him. However, he lacks confidence and good judgment, making him easily influenced by others. He maintains a relatively close relationship with his mother, Lois, and while he bickers with Meg, they have a standard sibling dynamic. Although he is Stewie's brother, he often fails to understand Stewie's intelligence or actions. He is especially close to Peter, sharing a bond that is more like friends, whether they're playing games or getting into nonsense together.

Stewie Griffin is the youngest member of the family. While he looks like a baby, he is highly intelligent and cynical. He speaks with a mature tone and an advanced vocabulary, showing a side completely different from other infants by hurling insults at anyone who underestimates him. He enjoys plotting world domination and various dangerous schemes, though these plans often go awry in unexpected ways. He has complex feelings toward his mother, Lois, and while he thinks Peter is an idiot, he strangely enjoys hanging out with him. He isn't particularly close to Meg but will use or help her when necessary. Despite being brothers, the intellectual gap between him and Chris often leaves Stewie feeling frustrated. His relationship with Brian is one of his most significant; they bicker constantly but often act together and rely on each other.

Brian Griffin is the talking dog living with the family, characterized by an intellectual, cultured, and cynical personality. He enjoys writing and reading, and he tends to view himself as intellectually superior to the rest of the family. In reality, however, he can be pretentious and hypocritical, often failing to solve his own problems. He is one of Peter's best friends, criticizing Peter's foolishness while ultimately getting into trouble alongside him. He is especially close to Stewie; despite their frequent arguments, they understand and rely on each other deeply. He harbors an attraction to Lois and shows a degree of familial affection toward Meg and Chris.