During the cataclysmic destruction of Krypton, a young Kryptonian Labrador Retriever, Krypto, provides solace to the infant survivor Kal-El as they escape aboard a pod en route to Earth.
Fast forward several years, and these two heroes, now known as Krypto and Superman, reside in Metropolis under their superhero identities, Bark and Clark Kent. Clark works as a reporter for the Daily Planet and is romantically involved with Lois Lane (Olivia Wilde), which causes jealousy in Krypto, especially when he feels Clark pushes him aside during their time together.
To help alleviate Krypto's loneliness, Clark visits an animal shelter to find him a companion. There, he encounters a Boxer named Ace, who attempts to flee because he dreams of going to a freedom-filled place he calls "the farm." Krypto intervenes, learning that Clark is looking for a friend for him, which only deepens his sadness.
The tension escalates when they spot their nemesis, Lex Luthor, CEO of LexCorp, who is attempting to seize an orange kryptonite meteor using a tractor beam to gain superpowers. Luckily, they defeat him with the help of the Justice League, which includes Wonder Woman, Green Lantern, Aquaman, Cyborg, The Flash, and the ever-watchful Batman. However, during the skirmish, Lex cunningly manages to secure a fragment of the orange kryptonite.
In a twist, an intelligent and villainous guinea pig named Lulu escapes from LexCorp with the same fragment, having obtained the ability to fly and employ telekinesis thanks to her new powers. She orchestrates a daring escape, leading a kitten named Whiskers along with her, abandoning the rest of the animals in the shelter.
Unbeknownst to Lulu, the other animals gain superpowers as well: Ace becomes super-strong, PB (Vanessa Bayer) transforms in size, Merton (Natasha Lyonne) finds incredible speed, and Chip (Diego Luna) gains electrokinesis.
The plot thickens when Superman proposes to Lois, leading to a fateful conflict with Krypto, who is later captured by Lulu. Using green kryptonite, she robs Clark of his powers. In his vulnerability, Krypto meets his father, Dog-El (Keith David), through a hologram from his collar, who inspires him to keep fighting for Superman.
Krypto eventually gathers the shelter pets, convincing Ace to assist him after leveraging Ace's own secrets about a "farm." While Lulu unleashes mayhem over the Justice League, the shelter pets and Krypto set out on their daring mission to thwart her plans and rescue Superman.
Together, they face the challenges posed by Lulu and her newfound henchmen, who challenge them to confront their fears and work as a cohesive team. Tensions rise when Lulu decides to become the embodiment of her powers, turning into a massive creature to eradicate her foes. Krypto, with his friends' support, must make a monumental choice between saving the Justice League or rescuing Lois, culminating in a spectacular showdown that tests their strength and resilience.
Ultimately, as Krypto performs the high-risk "Solar Paw Punch," an explosion arises, freeing him from inevitable doom and facilitating a vital defeat of Lulu. With the battle concluded, Krypto grants Clark the chance to marry Lois, and the former shelter pets find their forever homes with the Justice League.
As time passes, these animals evolve into their own vigilante team, aptly named the "League of Super-Pets." In the mid-credits scene, we find Luthor still imprisoned, pleading for liberation, and in a humorous twist during the post-credits, Krypto tricks Black Adam into an unexpected detour to Pluto.
