In 1964 England, Estella is a creative child with a talent for fashion, but is ostracized for her black and white hair and develops a nefarious streak. Her mother, Catherine, decides to move them to London, stopping at a party at Hellman Hall to ask the host for money. Sneaking inside, Estella loses her mother’s necklace while being chased by the host’s ferocious Dalmatian dogs, which push Catherine off a cliffside balcony to her death. Orphaned, Estella runs away to London and befriends street urchins Jasper and Horace.
Ten years later in 1974, Estella practices thievery and grifts with Jasper and Horace, honing her fashion skills by designing their disguises, alongside their dogs, Buddy and Wink. For her birthday in 1977, Jasper and Horace get her a job at the Liberty department store, but Estella is made a janitor and denied the chance to use her talents. She drunkenly redecorates the window display and impresses the Baroness—a renowned but authoritarian haute couture designer—who offers her a coveted job at her fashion house.
Estella gains the Baroness’s confidence but notices her wearing Catherine’s necklace, which the Baroness claims is a family heirloom that an employee once stole. Estella asks Jasper and Horace to help retrieve the necklace during the Baroness’s Black and White Ball.
To conceal her identity, Estella creates an alter-ego, “Cruella”, and wears one of the Baroness’s old designs from a vintage clothing store owned by the flamboyant Artie. At the ball, Cruella steals the spotlight as Jasper and Horace break into the Baroness’s vault, but she is already wearing the necklace. Jasper releases rats into the party, allowing Estella to swipe the necklace. The Baroness summons her Dalmatians with a dog whistle, and Estella realizes the Baroness caused Catherine’s death.
In the ensuing chaos, one of the Dalmatians swallows the necklace. Seeking revenge, Estella orders Jasper and Horace to kidnap the Dalmatians, and recovers the necklace. Cruella upstages the Baroness at various events in extravagant fashions, gaining notoriety via society columnist Anita Darling, Estella’s childhood friend. Furious, the Baroness fires her lawyer, Roger Dearly, while Cruella’s increasingly haughty behavior discomforts Jasper.
Estella designs and sews an elaborately beaded dress as the signature piece for the Baroness’s spring collection and stages a robbery in the fashion house, leading the Baroness to lock up all the dresses. The night of the spring show, the Baroness opens the vault to find that the entire collection has been destroyed by thousands of moths, having emerged from the beads on the dress which were actually moth cocoons. Seeing what she has done, the Baroness realizes Estella and Cruella are the same person. Having wrecked the Baroness’ show, Cruella stages her own fashion show outside in Regent’s Park, wearing a faux Dalmatian-fur coat.
Returning home, Estella is confronted by the Baroness and her men, who have captured Jasper and Horace. Setting fire to the building, the Baroness leaves Estella to die, and has Jasper and Horace sent to prison for her murder. Estella is saved by John, the Baroness’s valet, who reveals that the necklace unlocks a box containing Estella’s birth records: the Baroness is her biological mother. She had ordered John to murder the infant Estella to focus on her career and keep her late husband’s inheritance. Instead, John gave the baby to Catherine, one of the Baroness’s maids, who raised Estella in secret.
Cruella breaks Jasper and Horace out of prison and reveals the truth, recruiting them, Artie, and John for her final scheme. The quintet sneaks into the Baroness’s charity gala, having arranged for all the guests to dress as Cruella. Estella confronts her mother on the balcony, and the Baroness feigns an embrace before pushing her over the cliff, unwittingly witnessed by her guests. Estella secretly survives with a hidden parachute and, now legally dead, adopts her Cruella persona for good. The Baroness is arrested, swearing revenge on Cruella. Before her “death”, Estella willed her inheritance to Cruella, including the manor which she renames it from Hellman Hall to “Hell Hall”, moving in with her accomplices. In a mid-credits scene, Anita and Roger each receive a Dalmatian puppy from Cruella.