In the classic comic tradition of sidekicks, Hobbes represents Calvin's potential maturity and externalized conscience. A comic about a young boy throwing slushballs into a neighbor girl's head would be sad and trite without Hobbes there to wisely tease him, "You think she's cute, right?"

From everyone else's point of view, Hobbes is Calvin's stuffed tiger. From Calvin's point of view, however, Hobbes is an anthropomorphic tiger, much larger than Calvin and full of his own attitudes and ideas.

Hobbes' intangibility is called into question, however, when he pounces on Calvin (often leaving Calvin disheveled) and in one incident, ties him to a chair in such a way that his father is unable to understand how he could have done it himself. Also, in a very early strip, Calvin says that Hobbes ate a classmate of his (and Hobbes seems to verify this.) No other reference to Hobbes doing anything to another person is ever made.

Hobbes is much more rational and aware of consequences than Calvin, but seldom interferes with Calvin's troublemaking beyond a few oblique warnings—after all, Calvin will be the one to get in trouble for it, not Hobbes. Hobbes also has the habit of regularly stalking and pouncing on Calvin, most often when Calvin returns home from school. Hobbes is sarcastic when Calvin is being hypocritical about things he dislikes.

Susie Derkins is a classmate of Calvin who lives in his neighborhood. In contrast to Calvin she is polite and diligent in her studies, and her imagination usually seems mild-mannered and civilized, consisting of games such as playing "house" or having tea parties with her stuffed animals.

Susie and Calvin's relationship is a constant source of tension; she is frequently the victim of Calvin's derision and plots, and is also often willing to retaliate when provoked. Most commonly, Susie will be the target of Calvin's water balloons or snowballs, and he often goes to great lengths to disgust or annoy Susie. Calvin founded his and Hobbes' secret club, G.R.O.S.S. (Get Rid Of Slimy GirlS) as a general anti-girl organization, but in practice the club is almost invariably dedicated to pestering Susie specifically.

On occasion, Hobbes takes action to attract Susie's romantic attention, often with success, and much to Calvin's chagrin. Although on the surface these scenarios take the form of Hobbes teasing Calvin and showing off his charms, they may be Calvin's way to disguise his own crush on Susie, by pretending that it is Hobbes' crush instead. As Calvin once said, "It's shameless the way we flirt."

Spiff, "interplanetary explorer extraordinaire," explores the outermost reaches of the universe ("by popular request") in a red flying saucer with a bubble canopy. Spiff wears square glasses, or goggles, whose front openings change their shape according to his emotions.

The galaxy is a cruel place where Spiff is often zapped, shot down, or captured by ferocious and disgusting aliens (who, in reality, are people such as Calvin's parents, Miss Wormwood, etc.), stranded in a desert, on a planet, or both. Most planets seem devoid of civilization, and often have hostile environments or alien predators.

Calvin's father is a patent attorney who is portrayed as an upstanding middle-class father, as his son might see him. An outdoorsman, he enjoys bike rides and camping trips, and insists that these activities, like Calvin's chores, "build character." When Calvin asks him questions, he often makes up outlandish answers, such as:

Calvin: "Why does it [the sun] move from east to west?"
Dad: "Solar wind."
Mom: "DEAR!"

or

Calvin: "Dad, what makes wind?"
Dad: "Trees sneezing."
Calvin: "Really?"
Dad: "No, but the truth is more complicated."
Calvin (later, to Hobbes): "The trees are really sneezing today."

or

Calvin: "Dad, why are old photographs black and white? Didn't they have color film back then?"
Dad: "Of course they did. In fact, those old photographs ARE in color. It's just that the WORLD was black and white then.
Calvin:"Really?"
Dad: "Yep, the world didn't turn color until sometime in the 1930s, and it was pretty grainy color for a while, too.
Calvin:"Oh."
Dad: "Well, truth is stranger than fiction."
Calvin: "Then why are old paintings in color? If the world was black and white, wouldn't artists have painted that way?"
Dad: "Not necessarily. A lot of great artists were insane."
Calvin: "BUT... but how could they possibly have painted in color? Wouldn't their paints have been in shades of gray back then?"
Dad: "Of course, but they changed color like everything else in the '30s.
Calvin: "So why didn't black and white photos turn color too?"
Dad: "Because they were color photographs of black and white, remember?"

Of course, these bits of nonsensical fatherly "wisdom" may also signify that Calvin's father, like Calvin himself, has an imaginative streak that occasionally bursts free of his straightlaced paternal façade (thus implying that Calvin's mother's occasional accusations that Calvin must have inherited his outlandish behavior from Dad's side of the family may, in fact, be correct).

This playful streak of his allows him to occasionally find moments of solace with Calvin, and it is implied that Calvin's Dad may have been like Calvin in his youth, such as in the strip in which Calvin's Dad shows a surprising understanding of Calvin's impatience, and has subsequently matured and developed a more pensive character. This lends a pleasant optimism to the strip, as it is possible that Calvin's obvious intelligence may someday be understood by society and put to good use, and he will become a well-rounded character like his dad. This, of course would mortify Calvin if he were to read it, as he himself, in his youthful jubilance, describes his traditionalist father as "the most boring Dad in the world."

Miss Wormwood is Calvin's world-weary teacher. She perpetually wears polka-dotted dresses, and is another character who serves as a foil to Calvin's mischief. Calvin, when in his Spaceman Spiff persona, sees Miss Wormwood as a slimy, often dictatorial alien.

Calvin's mother is a stay-at-home parent who is frequently exasperated by Calvin's antics. Prior to Calvin's birth, she worked a stressful job filled with aggravation, which Calvin's father claims is the reason she was better prepared to stay at home and raise Calvin. Whether he was jesting or not is debatable. On the rare occasions when she is not reacting to Calvin's misbehavior, she seems to enjoy quiet activities, such as gardening and reading The "Daily Disciplinarian."

She is frequently the one forced to curb Calvin's destructive tendencies; once she allows Calvin to smoke a cigarette in order to teach him how unpleasant smoking can be. She also usually seems sympathetic towards her son's relationship with Hobbes, and a few times has found herself speaking to Hobbes as well (although she refers to one instance as "talking to a stuffed animal").

Although Calvin's behavior drives his mother crazy (Calvin once quipped "another day, another gray hair for Mom!"), she still loves him very much. When Calvin was lost on a trip to the zoo, she became sick with worry, and was thrilled when his dad brought him back.
She has also stepped in when his father goes too far with his own private jokes, going so far as to say "I know somebody who's going to get a lot of coal in his stocking, buster." She frequently scolds her husband for his sarcasm in dealing with their son.
Finally, she is sometimes able to calm Calvin down when he is in a bad mood, offering peanut-butter crackers, comic books and other treats to cheer him up

Once Calvin acted as Safari Al, a jungle explorer, and discovered a "giant gorilla". The gorilla turned out to be Calvin's mom stating "clean your room, it's a jungle in here".

Mr. Spittle is the headmaster at Calvin's school. Calvin often gets sent to his office by Miss Wormwood for various reasons ranging from daydreaming to harassing Suzie in class.