Hopps abandons her shift to arrest a thief, Duke Weaselton. She is reprimanded by Bogo and nearly fired until Mrs. Otterton, an otter, arrives pleading for help locating her missing husband – one of many animals recently missing in Zootopia. To Bogo's dismay, Hopps volunteers and agrees to resign if she cannot solve the case within 48 hours. She sees Wilde in the last known photo of Otterton and tracks him down, coercing him into to assisting her with the investigation.
After acquiring Mr. Otterton's license plate number, Hopps and Wilde track the vehicle to Mr. Big, an Arctic shrew crime boss. Mr. Big informs the pair that Otterton, his florist, had gone savage and attacked his chauffeur Manchas, a black jaguar. Hopps and Wilde locate Manchas, who mentions "night howlers" were responsible for attacking him before he goes savage and chases the pair out of his home. When Bogo and his reinforcements arrive, Manchas disappears. Bogo demands Hopps resign, but Wilde takes a stand, insisting they have 10 more hours to solve the case. As the pair leaves, Hopps learns from Wilde that he was bullied by prey animals as a pup and became a criminal, believing he would be stereotyped as one no matter what due to being a fox.
Wilde realizes that the city's traffic camera system may have captured Manchas's disappearance, and the pair consult Assistant Mayor Bellwether, a sheep. They identify the captors as wolves, hence "night howlers". Hopps and Wilde locate the missing mammals (including Mr. Otterton) at Hillside Asylum. All are predators, and all have gone savage like Manchas. The two discover Mayor Lionheart consulting with a doctor about the predators' condition. The pair escape with the evidence and the police swarm the area, arresting Lionheart.
Having developed a friendship with Wilde throughout the case, Hopps requests that he joins the Zootopia Police Department and become her partner, which Wilde happily considers. However, during a press conference, Hopps mentions that the savage animals are predators and argues they have gone back to their "natural state." Wilde is hurt and angrily walks out on her offer. Fear and discrimination against predators spreads across Zootopia, and a guilt-ridden Hopps resigns. During this time, pop singer Gazelle holds a peaceful protest and publicly asks for the harmonious Zootopia she loves to be restored.
Back in Bunnyburrow, Hopps learns that "night howlers" are flowers that have a severe psychotropic effects on mammals. Hopps returns to Zootopia and reconciles with Wilde. They locate Weaselton and learn that he has been collecting night howlers for a secret laboratory. The pair discover the lab and find ram scientists creating a night howler serum, which has been injected into predators via dart guns. Hopps and Wilde race to the ZPD with the evidence, but the rams pursue them.
Just short of the ZPD, the pair encounters Bellwether, who tries to take the evidence. Realizing Bellwether is the mastermind of a species-supremacist conspiracy, Hopps and Wilde try to flee, but Bellwether shoots a dart at Wilde and calls the ZPD for help. Wilde becomes savage and corners Hopps, but it turns out the pair were acting and had swapped out Bellwether's darts for blueberries. With Bellwether's confession recorded on Hopps's carrot pen, the two have enough evidence to unravel the conspiracy.
Some months later, Hopps is reinstated into the ZPD. The savaged mammals are cured. Lionheart is cleared of all charges and is reinstated as mayor. Wilde joins the ZPD as the first fox officer and Judy's new partner. In the final scene, all of Zootopia enjoys a performance by Gazelle, who dances with four tigers.