Fisherman Matthew Boyd (Richard Dreyfuss) is enjoying a day at Lake Victoria, Arizona, serenading the waters with a whistled rendition of Show Me the Way to Go Home, a nostalgic homage to Jaws. However, the tranquility is abruptly shattered when a tremendous earthquake strikes, opening an immense underwater trench that unleashes a torrent of piranha fish from the depths. As chaos unfolds, Matt finds himself thrown into the fray, where he meets a gruesome fate, devoured by the ravenous school of piranha, leaving behind a mangled body that signals trouble ahead.
As spring break descends upon Lake Victoria, the local sheriff, Julie Forester (Elisabeth Shue), grapples with the challenges of managing a wave of intoxicated college students while responding to recent earthquake reports. Her 17-year-old son, Jake (played by Steven R. McQueen), witnesses his mother arrest a rowdy frat-boy while he is enchanted by the spring break atmosphere. On his way to pick up his 10-year-old sister, Laura (Brooklynn Proulx), from music class, Jake encounters Kelly (Jessica Szohr), a local girl he has a crush on. Kelly invites him to a backstage party at a concert, courtesy of the local bully, Todd. Unfortunately, Todd's cruel antics foil Jake's attempts to connect with Kelly when he douses Jake with a slushy, prompting Kelly to leave with Todd.
Meanwhile, Derrick Jones (Jerry O'Connell), a porn director, is in town for a shoot alongside glamour model Danni (Kelly Brook). Jake, drawn into their world by chance, finds himself working as Derrick's location scout, intrigued by the promise of a day's pay. Later that evening, Julie and Deputy Fallon (Ving Rhames) investigate the disappearance of Matthew Boyd. Upon stumbling upon Matt's empty boat and later his body, they consider closing the lake to protect the public.
The following day, as Julie and Fallon accompany a team of seismologists to explore the newly exposed chasm, diver Sam (Ricardo Chavira) discovers thousands of unhatched piranha eggs lurking below. In a twist of fate, Sam is attacked and bleeds into the water, drawing the piranhas out once more. In a desperate attempt to save his colleague, team leader Novak (Adam Scott) jumps in, but tragedy strikes, resulting in a horrific revelation about the ancient piranha species that had been presumed extinct for millions of years. With this knowledge, the decision to evacuate Lake Victoria takes priority.
Meanwhile, Jake neglects his babysitting duties and makes a pact with Laura and Zane (Sage Ryan) to stay home while he participates in the craziness of Derrick's filming. When Laura and Zane decide to venture out in a canoe and find themselves stranded, Jake arrives just in time to rescue them aboard Derrick's boat, unaware of the impending danger lurking beneath the surface.
As the chaos escalates at the beach and the piranhas begin their merciless assault on unsuspecting partygoers, Julie and Fallon attempt to execute the evacuation plan, only to be met with resistance from the revelers reveling in the sun. The horrors unfold rapidly, with many falling victim to the aquatic predators, including cowardly Todd and even Fallon, who faces a dreadful fate.
Derrick, high on drugs, haphazardly steers the boat into a precarious position, leading to a devastating accident that leaves Kelly trapped below deck and the boat flooding with piranhas. In a frantic bid for survival, Jake communicates with his mother, who races to their rescue with Novak. As they make their daring save, the tension mounts when a massive explosion rips through the water, destroying the threatening piranhas on impact.
With Jake and Kelly barely escaping from the jaws of death, they find temporary relief alongside Julie and their siblings. However, their moment of triumph is short-lived as a shocking twist ensues: a gargantuan piranha, larger than ever imagined, leaps onto their boat, bringing their fight for survival back to the forefront.
