Main articles: Tom Cat and Jerry Mouse
Thomas "Tom" Cat.
Tom is a blue-grey British longhair cat. He is the main protagonist and also the main antagonist of the story, who lives a pampered life, while Jerry is a small brown house mouse who always lives in close proximity to him and he is the second protagonist of the story. "Tom" is a generic name for a male cat or Warner Bros. cartoon character Sylvester was originally called "Thomas". Tom was originally called "Jasper" in the very first short, Puss Gets the Boot, while Jerry was named "Jinx". Tom is very quick-tempered and thin-skinned, while adorable mouse Jerry is independent and opportunistic. Jerry also possesses surprising strength for his size, lifting items such as anvils with relative ease and withstanding considerable impacts with them. Despite the typical cat eats mouse, it is actually quite rare for Tom to actually try and consume Jerry. Despite being very energetic and determined, Tom is no match for Jerry's brains and wits. By the final "iris-out" or "fade-out" of each cartoon, Jerry usually emerges triumphant, while Tom is shown as the loser. However, other results may be reached; on rare occasions, Tom triumphs, usually when Jerry becomes the aggressor or when he crosses some sort of line (the best example of which occurs in The Million Dollar Cat where, after finding out that Tom's newly acquired wealth will be taken away if he harms any animal, including a mouse, he torments Tom until Tom finally loses his temper and attacks him). Sometimes, usually ironically, they both lose, usually when Jerry's last trap potentially backfires on him after it affects Tom (An example is in Chuck Jones' Filet Meow short where Jerry orders a shark to scare Tom away from eating a goldfish. Afterwards, the shark scares Jerry away as well) or when Jerry overlooks something at the end of the course. Sometimes, they both end up being friends (only for something to happen so that Tom will chase Jerry again). Both characters display sadistic tendencies, in that they are equally likely to take pleasure in tormenting each other. However, depending on the cartoon, whenever one character appears to be in mortal danger (in a dangerous situation or by a third party), the other will develop a conscience and save him. Sometimes, they bond over a mutual sentiment towards an unpleasant experience and their attacking each other is more play than serious attacks. Multiple shorts show the two getting along with minimal difficulty, and they are more than capable of working together when the situation calls for it, usually against a third party who manages to torture and humiliate them both.
Tom changes his love interest many times. The first love interest is Toots who appears inPuss n' Toots, and calls him "Tommy" in The Mouse Comes to Dinner. He is also interested in a cat called Toots in The Zoot Cat although she has a different appearance to the original Toots. The most frequent love interest of Tom's is Toodles Galore, who never has any dialogue in Tom and Jerry cartoons.
Despite five shorts ending with a depiction of Tom's apparent death, his demise is never permanent; he even reads about his own death in a flashback in Jerry's Diary. He appears to die in explosions in Mouse Trouble (after which he is seen in heaven) and in Yankee Doodle Mouse, while in The Two Mouseketeers he is guillotined offscreen.
Although many supporting and minor characters speak, Tom and Jerry rarely do so themselves. Tom, most famously, sings while wooing female cats; for example, Tom sings Louis Jordan's "Is You Is Or Is You Ain't My Baby" in the 1946 short Solid Serenade. In a couple of shorts, Tom, when romancing a female cat, woos her in a French-accented voice similar to that of screen actor Charles Boyer. At the end of The Million Dollar Cat after beginning to antagonize Jerry he says that he is throwing away a million dollars, but he is happy. Co-director William Hanna provided most of the squeaks, gasps, and other vocal effects for the pair, including the most famous sound effects from the series, Tom's leather-lunged scream (created by recording Hanna's scream and eliminating the beginning and ending of the recording, leaving only the strongest part of the scream on the soundtrack) and Jerry's nervous gulp. The only other reasonably common vocalization is made by Tom when some external reference claims a certain scenario or eventuality to be impossible, which inevitably, ironically happens to thwart Tom's plans - at which point, a bedraggled and battered Tom appears and says in a haunting, echoing voice "Don't you believe it!", a reference to some famous World War II propaganda shorts of the 1940s. In one episode, Tom hires a mouse exterminator who, after several failed attempts to dispatch Jerry, changes profession to Cat exterminator by crossing out the "Mouse" on his title and writing "Cat", resulting in Tom spelling out the word out loud before reluctantly pointing at himself. One short, 1956's Blue Cat Blues, is narrated by Jerry in voiceover (voiced by Paul Frees) as they try to win back. Both Tom and Jerry speak more than once in the 1943 short The Lonesome Mouse. Tom and Jerry: The Movie is the first (and so far only) installment of the series where the famous cat-and-mouse duo regularly speak.
 Spike and Tyke
Main articles: Spike (Tom and Jerry) and Tyke (Tom and Jerry)
Spike and his puppy son Tyke.
In his attempts to catch Jerry, Tom often has to deal with Spike (also known as "Killer" ), an angry, vicious but extremely dumb guard bulldog who tries to attack Tom for bothering his son Tyke (sometimes called "Junior") while trying to get Jerry. While they are in the cartoons, Tom and Jerry appears always while chasing and bothering his son. Originally Spike was unnamed and mute (aside from howls and biting noises) as well as attacking indiscriminately, not caring whether it was Tom or Jerry though usually attacking Tom. In later cartoons Spike spoke often, using a voice and expressions (performed by Billy Bletcher and later Daws Butler) modeled after comedian Jimmy Durante. Spike's coat has altered throughout the years between grey and creamy tan. The addition of Spike's son Tyke in the late 1940s led to both a slight softening of Spike's character and a short-lived spin-off theatrical series (Spike and Tyke). Most cartoons with Spike in it have a system; usually Spike is trying to accomplish something (such as building a dog house or sleeping) when Tom and Jerry's antics stop him from doing it, Spike then (presumably due to prejudice) singles out Tom as the culprit and threatens him that if it ever happens again he will do "something horrible" to Tom (effectively forcing Tom to take the blame of anyone else) while Jerry overhears, afterwards Jerry usually does anything he can to interrupt whatever Spike is doing while Tom barely manages to stop him (usually getting injured in the process), usually Jerry eventually wrecks whatever Spike is doing in spectacular fashion and leaving Tom to take the blame, forcing him to fight Spike and inevitably lose (usually due to the fact the Tom is usually framed by Jerry and that Spike just doesn't like Tom) off-screen, finally Tom is generally shown injured while Jerry smugly cuddles up to Spike unscathed. At least once however Tom does something that benefits Spike, who promises not to interfere ever again; causing Jerry to frantically leave the house and run into the distance (in Hic-cup Pup). Spike is well known for his famous "Listen pussy cat!" catchphrase when he threatens Tom, his other famous catchphrase is "That's my boy!" normally said when he supports or congratulates his son. Tyke is described as a cute, sweet looking, happy and a loveable puppy. He is Spike's son, but unlike Spike, Tyke does not speak and only communicates (mostly towards his father) by barking, yapping, wagging his tail, wimpering and growling. Tyke's father Spike would always get out of the way to care and comfort his son and make sure that he is safe from Tom. Tyke loves his father and Spike loves his son and they get along like friends, although most of time they would be taking a nap or Spike woluld teach Tyke the main facts of life of being a dog. Like Spike, Tyke's appearanch has altered throughout the years, from grey (with white paws) to creamy tan. When Tom and Jerry Kids first aired, this was the first time that viewers were able to hear Tyke speak.
 Butch and Toodles Galore
Main articles: Butch (Tom and Jerry) and Toodles Galore
Butch and Toodles Galore, in the 1946 Tom and Jerry short Springtime for Thomas.
Butch is a black alley cat who also wants to catch and eat Jerry. He is the most frequent adversary of Tom. However, for most of the episodes he appears in, he's usually seen rivaling Tom over Toodles. Butch also appeared as one of Tom's pals or chums as in some cartoons, where Butch is leader of Tom's buddies, who are Meathead and Topsy.