The movie kicks off with a newscast detailing the aftermath of the brutal attack on Lake Victoria by prehistoric piranhas. A year later, an intense eradication campaign has rendered the lake devoid of any life, leading to the town’s decline, as tourism—its main revenue source—disappears. With the beaches dried up and the piranhas eradicated, the fate of the original survivors remains a mystery.
In a nearby lake, Clayton and Mo brave the waters to retrieve the body of a dead cow, uncovering that dangerous eggs have been laid inside it. Oblivious to the lurking threat, they encounter a swarm of piranhas. Mo is viciously devoured, leaving nothing but his hat bobbing on the crimson surface, while Clayton fights valiantly, ripping a piranha off his face, only to be torn apart under the water.
Enter Maddy, a marine biology student played by Danielle Panabaker, who returns to her summer position at a waterpark co-owned with her sleazy step-father, Chet. Upon her arrival, Maddy is horrified to learn about Chet’s plans to transform the waterpark into an adult-themed venue, dubbed "Big Wet," complete with 'water-certified strippers.' The adult section is filled with nudity and debauchery, with one employee, Big Dave, taking things too far with hydraulic inflow pipes. At a chaotic party that night, Maddy bumps into friends—her policeman ex-boyfriend Kyle and childhood crush Barry—while navigating the bizarre scenes around her.
As events spiral out of control, Shelby and her boyfriend Josh decide on a romantic swim, but a piranha finds its way into Shelby’s vagina, leading to a shocking misunderstanding. Meanwhile, Ashley and her boyfriend Travis inadvertently find themselves in a perilous situation when their van plunges into the lake, leading to a horrifying sequence as piranhas attack them while Ashley desperately tries to escape.
The following day, Maddy and Shelby are attacked by piranhas while on a jetty, barely escaping with their lives. Maddy, alongside Kyle and Barry, seeks help from Mr. Goodman, who conducts experiments to understand the piranha behaviors deeper, revealing their potential to move between lakes through sewage systems. Maddy bravely swims to check the safety grates, narrowly evading another attack.
As chaos looms, Shelby, convinced she's dying, urges Josh to have sex with her. But as piranhas invade their intimacy, Josh is forced to take a drastic measure to free himself from a deadly bite. Meanwhile, Chet’s underhanded dealings and Kyle’s corrupt actions begin to unfold as the waterpark gears up for its grand opening, infested with piranhas eager to feast on the unsuspecting clientele.
During this tumultuous event, David Hasselhoff makes a formidable appearance as a celebrity lifeguard. Amidst the chaos, Deputy Fallon, who survived a previous piranha encounter, takes matters into his own hands by fashioning a shotgun prosthesis, battling the undead menace in the water.
As the situation escalates, Maddy’s efforts culminate in a frantic race against time to stop the piranhas. In an explosive showdown, lives are lost, and shocking reveals emerge, including the awakening of the piranhas' evolutionary abilities. In a harrowing final scene, a piranha leaps out of the pool with deadly intent, claiming yet another victim, the young boy who simply wanted a picture.
The film concludes with a chilling reminder that the terror is far from over, teasing an ominous future as the piranhas adapt and threaten all who dare approach the water once more.
