Middle-aged best friends Barb and Star leave their home of Soft Rock,
Nebraska for the first time to go on vacation to Vista Del Mar,
Florida. They are apprehensive about trying something new. The two friends construct a narrative about a woman named "Trish", who becomes a water spirit. Upon arrival, they find accommodations at the luxurious Vista Del Mar Hotel and resolve to try many excursions, particularly an inflatable banana
inner tube ride. Meanwhile, an eccentric villain, Sharon Fisherman is plotting against the denizens of Vista Del Mar. Sharon lived there as a child, and her pale white skin and sensitivity to the sun made her an outcast and a target of bullying. She plans to unleash lethal mosquitos, killing everyone. She sends her henchman, Edgar, to Vista Del Mar to plant a
homing beacon that will attract the mosquitos once they are unleashed. She falsely promises Edgar that if he succeeds, she will finally make their relationship official. Barb and Star encounter Edgar at the hotel bar and begin to bond and party with him. The next morning, Edgar realizes he lost the microchip for the beacon during the night, infuriating Sharon. She sends another agent, Darlie Bunkle, to give Edgar another microchip and to spy on him, Barb, and Star. Barb meets with Edgar, but feels conflicted about seeing him behind Star's back, and decides not to pursue him any further. Star also meets with Edgar, but despite feeling conflicted about Barb, continues to have a sexual relationship with him in secret that develops into romance. Star's secret tryst leaves Barb alone at the resort, and Barb tries out all Vista Del Mar has to offer. On the day of the annual Seafood Jam, she decides to wait for Star before going on the banana ride, but spots Star and Edgar having sex on Edgar's balcony. She goes to confront Edgar, but overhears his plans with Sharon. She informs Star, who accuses her of jealousy, while Barb accuses her of lying to her. Sharon uses photos from Darlie to convince Edgar that Barb and Star are spies and that Star was using him. She orders him to kill them. Edgar captures them but cannot bring himself to kill them, leaving them indoors where they will be safe and plants the beacon. They escape, but are kidnapped by Sharon, who brings them to an ocean cliff. She forces the women to jump, and leaves to go ensure her revenge succeeds. As they fall, Barb and Star's
culottes act as parachutes that allow them to safely land on the ground. They reconcile and go to stop Sharon. Edgar realizes that Sharon lied to him about Barb and Star, that she never loved him, and was setting him up to die. He spots Star and Barb and helps them locate the homing beacon. He confesses his love to Star, but they are held at gunpoint by Darlie. Edgar fights Darlie, while Star and Barb escape with the beacon, taking a
jet ski out to sea to save the town. Sharon uses a
human cannon to reach them, regaining the beacon. However, it is too late and the unleashed mosquitos converge on her. Barb and Star go underwater, avoiding the mosquitos. They are rescued and brought back to shore by Trish, the water spirit. Sharon arrives on shore, having survived the mosquitos by taking an
antidote. Star recognizes that Sharon's hostility is born from her bullied childhood, and having never experienced true friendship (with the exception of a girl who befriended her only to be immediately eaten by an alligator). She offers to be Sharon's friend, as do the other residents, melting Sharon's icy facade. The town celebrates. Barb and Star ride the banana ride for hours. Yoyo arrives at the beach and initiates a celebration. ==Cast==