Jerry is a "minor celeb" stand-up comedian who is often depicted as "the voice of reason" amidst the general insanity generated by the people in his world. The in-show character is a mild germaphobe and neat freak, as well as an avid Superman, New York Mets and breakfast cereal fan. Jerry's apartment is the center of a world visited by his eccentric friends and a focus of the show.

George is Jerry's best friend, and has been since high school. He is dishonest, petty and envious of others' achievements. He is depicted as a loser who is perpetually insecure about his capabilities. He complains and lies easily about his profession, relationships and almost everything else, which usually creates trouble for him later. He often uses the alias Art Vandelay when lying or concocting a cover story. Despite these shortcomings, George has a sense of loyalty to his friends and success in dating women and eventually secures a successful career as Assistant to the Traveling Secretary for the New York Yankees. He is thought to be a fictional version of show's creator, Larry David.

Elaine is Jerry's ex-girlfriend and friend. She is humorous, arrogant and occasionally impulsive. She sometimes has a tendency to be too honest with people (usually by losing her temper), which often gets her into trouble. She usually gets caught up in her boyfriends' quirks, eccentric employers' unusual behaviors and idiosyncrasies, and the maladjustment of total strangers. She tends to make poor choices in men she chooses to date and is often overly reactive. First she works at Pendant Publishing with Mr. Lippman, is later hired as a personal assistant for Mr. Pitt, and later works for the J. Peterman fashion catalogue as a glorified assistant. Elaine is popularly described as an amalgamation of David's and Seinfeld's girlfriends during their early days in New York as struggling comedians.

Kramer is Jerry's lovable but odd neighbor. His trademarks include his humorous upright pompadour hairstyle, vintage clothes, and energetic sliding bursts through Jerry's apartment door. Kramer was heavily based on a neighbor of David's during his amateur comedic years in Manhattan. At times, he appears naïve, gullible, and ignorant, and at other times, intelligent, understanding, and well-read; similarly, he is exaggeratedly successful, socially, with his charisma and laid-back personality. This is seen in his success with women and employers. He has been described as a "hipster doofus". Although he never holds a steady job, he is rarely short of money and often invents wacky schemes that often work at first then eventually fail.

A fellow tenant in Jerry and Kramer's apartment building. A bulky male U.S. postal worker and Jerry's nemesis. A catchphrase of Jerry's is that he greets him with a contemptuous disdainful "Hello, Newman" each time they meet.

George's father, utterly deranged and very quick to anger. Of Italian descent, he was a travelling businessman who detests removing his shoes in other people's homes, and wears his sneakers in the swimming pool.

George's highly obnoxious and melodramatic Jewish mother. She constantly squabbles with Frank and George about their actions, but is the closest thing to reason in the Costanza household. Enjoys playing Mahjong. George claims she has never laughed, ever.

Jerry's father, has strong, if sometimes outdated convictions about business and the way of the world. Fittingly, he spent some time as a politician in his Florida retirement community. During his working years, he sold raincoats with Harry Fleming and was the inventor of the "belt-less trench-coat." He hates Velcro because of "that tearing sound."

Jerry's mother, often needed to provide reason to Jerry's and Morty's eccentric lifestyle, though overprotective of Jerry and often refuses point-blank to do anything that would place him at inconvenience. She is the only secondary character to appear in all nine seasons.