Thomas "Tom" Cat (originally known as Jasper in Puss Gets the Boot) is one of the two protagonists in Tom and Jerry, created by William Hanna and Joseph Barbera. He is an adult bluish-gray anthropomorphic domestic short-haired cat who first appeared in the 1940 animated short Puss Gets the Boot. Tom was originally known as Jasper during his debut in that short, however, beginning from his next appearance in The Midnight Snack and onwards Thomas "Tom" was used. In the 2021 live action movie, Tom's full name was revealed to be Thomas D. Cat. In the fighting game MultiVersus, Tom's full name was given as Thomas Jasper Cat Sr.

Jerry Mouse (originally known as Jinx) is a fictional character and is one of two protagonists in Metro-Goldwyn Mayer's series of Tom and Jerry theatrical cartoon short films. Created by William Hanna and Joseph Barbera, he is a cute young brown house mouse, who first appeared as an unnamed mouse in the 1940 MGM animated short Puss Gets the Boot. Hanna gave the mouse's original name as Jinx, while Barbera claimed the mouse went unnamed in his first appearance. In the 2021 movie, his full name is revealed to be Jerome A. Mouse. In the fighting game MultiVersus, Jerry's full name is said to be Gerald Jinx Mouse.

Spike (occasionally referred to as Butch or Killer) and Tyke are fictional characters from the Tom and Jerry series, created by William Hanna and Joseph Barbera. Spike is a stern but occasionally dumb British bulldog who is particularly disapproving of cats, but a softie when it comes to mice, and later, his son Tyke. In the shorts Jerry would often try to get Tom in trouble with Spike making him a shoo-in for a beating from the bulldog. Spike has a few weaknesses that Tom tries to capitalize upon: his possessiveness about his bone and his ticklishness. He made his first appearance in the 1942 Tom and Jerry cartoon Dog Trouble, and his first speaking role was in 1944's The Bodyguard, where he was voiced by Billy Bletcher up until 1949, from which point he was voiced by Daws Butler. Tyke is known as a cute, sweet, happy and a loveable pup. He is Spike's son, and they make the perfect father and son, with Spike spending much of his free time comforting his son, taking him out or teaching him the facts of life of being a dog. In Tom and Jerry Kids, Tyke has a speaking role and was the first time that Tom and Jerry fans were able to hear Tyke speak. They both appear in shows and movies with a red and yellow spiked collar and grey fur with a light pink chest.

Toots is a female cat character first introduced in "Puss N' Toots" Episode.