Brian is a talking dog who was born in Austin, Texas and has lived with the Griffin family since Peter picked him up as a stray. While he exhibits some typical dog behaviors such as eating garbage and being afraid of the vacuum, he also possesses various anthropomorphic qualities, such as the ability to speak intelligently and attending college. He also has a particularly sharp wit. Peter is his best friend, despite Brian's vastly superior intelligence. Seth MacFarlane has once described Brian as "a dog who has a wit as dry as the martinis he drinks."[citation needed] Brian is often the voice of reason in the family, frequently reminding Peter how stupid his plans are.

Brian is an atheist who often gets irritated when confronted with religious intolerance atau blind faith.

Brian has a cultured background; he loves opera and jazz, has talented vocal ability, being able to sing all four parts to a barbershop quartet simultaneously. He attended Brown University, and is an avid writer. Brian also has aspirations as a novelist, and fleeting mentions of his novel are a running gag on the show.

While not seen holding a regular job in Quahog, Brian is depicted both owning and driving a silver Toyota Prius, paying bills, and maintaining a credit card. In various episodes, he has been a substitute teacher at Chris's school, a contributor for the The New Yorker, a taxi driver, and a drug-sniffing dog for the Quahog police department. He also worked selling cars while the Griffin family thought that Peter had died in the episode "Perfect Castaway". Brian held several jobs while living in Los Angeles including waiter, car wash attendant, screenwriter, and pornographic film director.