[1] It chronicles the daily lives of an ensemble cast of suburban anthropomorphic animals: Pig, Rat, Zebra, Goat, and a fraternity of crocodiles,[2] as well as a number of supporting characters, one of whom is Pastis himself.

Pastis recalled in 2009: United signed me in December 1999, and they put me in development ... where the syndicate says, OK, you were funny in your submission packet, but for all we know, it took you 10 years to come up with these 30 strips.

[9][10] In January 2021, Andrews McMeel delayed the circulation of a comic arc that depicted a fictional American coup d'état, worrying that readers might think of it as inspired by the 2021 United States Capitol attack.

[11] Pearls's style and humor are inspired by several comic strips, chiefly Peanuts, Dilbert, Calvin and Hobbes, Bloom County and The Far Side.

Pig's lack of knowledge often leads him to misunderstand world issues and social norms; this is compounded by the fact that, when they are explained to him, he frequently mishears or misinterprets important parts of the explanation.

On several occasion, he has befriended sentient food items; he has also dated a maple syrup bottle named "Ms. Bootyworth" and founded a religion centered on cheese.

In addition to his voracious eating habits, Pig is generally slothful and avoids physical activity, causing him to be obese.

While he is generally content with his body, he occasionally attempts to lose weight; however, he usually takes only minimal efforts to do so.

(Pastis also said this was a play on a Biblical verse, part of which reads "neither cast ye pearls before swine".)

[15] In addition to his arrogance, Rat is high-strung and impatient, and frequently unleashes angry tirades, physical violence, or elaborate revenge plots against people who anger him.

Recurring characters in Rat's writing include Angry Bob, a character who tends to die violently while pursuing happiness and inner peace; Elly Elephant and Henry Hippo, who typically appear in cynical parables about romance; and a nameless, corrupt congressman.

Though Rat seems to dislike or disdain everyone he meets – including his family, who he generally strives to avoid whenever possible – he does occasionally show moments of kindness.

'"[21] Rat has also nursed romantic feelings for Pig's sister Farina during her rare appearances in the strip.

Despite his intellect and his generally amiable personality, Goat tends to be socially inept – he is usually uncomfortable around new people, and has fairly little knowledge of pop culture.

For this reason, while Goat regularly pursues romantic relationships, his efforts tend to be sabotaged by his awkward behavior.

He was originally supposed to be a bear, but after the syndicates rejected the idea Pastis reworked the character into a goat.

In his earliest appearance, Zebra only communicated with his predators by sending letters back and forth, but he began interacting with them face-to-face after the fraternity of crocodiles moved into his neighborhood in January 2005.

[26] Zebra generally serves as a straight man to the crocodiles' schemes, pointing out the various ways in which their plots to eat him are doomed to fail.

Zebra also owns a pet cat named Snuffles, who commits a wide variety of crimes despite his innocent appearance.

They consistently make attempts to kill and eat Zebra but, despite believing themselves to be capable hunters, the crocodiles always undermine their schemes due to their collective stupidity.

[29] The crocodiles' plans are often elaborate and convoluted, but even so, they never successfully conceal the fact that their ultimate goal is to capture and eat Zebra.

In describing the origin of the crocodiles' speech, Pastis has stated, "My inspiration was probably from a Saturday Night Live skit that had Tarzan and Frankenstein trying to talk [to each other]."

[30] Larry is also egotistical and defensive about his hunting abilities; he tries to portray himself as a skilled hunter and provider, but to keep up this impression, he frequently perpetrates schemes such as claiming fast food products to be zebra meat.

Junior is a studious and highly intelligent young crocodile; he is also a pacifist and a vegetarian, as he thinks that killing wildlife is immoral.

Initially simply a violent, sociopathic duck, he later took on the persona of a jaded soldier and mercenary, seeing the world as his battlefield.

Pastis has emphasized that Guard Duck has a predominantly "cool persona" in that, while he is prone to violence, he does not "freak out or panic".

Guard Duck frequently collaborates with Zebra's amoral pet cat, Snuffles, to perpetrate criminal schemes and occasional coups d'etat.

Pearls uses dark humor, at times involving topics such as death, depression and human suffering.

In an interview on The Big Idea with Donny Deutsch that aired on February 7, 2008, Pastis mentioned that he had been approached by producers about an animated TV series based on Pearls.

Pastis won the National Cartoonists Society's Division Award for Best Newspaper Comic Strip for Pearls in 2003, 2006 and 2014.