Fin Shepard and his ex-wife April Wexler are flying to New York City to promote How to Survive a Sharknado and Other Unnatural Disasters, a book April has written about the Los Angeles sharknado. As the plane comes in for a landing through a storm, it is battered by airborne sharks, losing an engine. Sharks enter the plane, killing passengers and crew, including both pilots. While Fin lands the plane, April's hand is bitten off by a shark while she attempts to shoot it with an air marshal's handgun.
Fin's sister, Ellen Brody, is sightseeing in New York with her family. Her husband, Martin, a childhood friend of Fin's, takes their son, Vaughn, to a Mets game at Citi Field along with Martin's and Fin's friends Skye (a former love interest of Fin's) and Brian. Ellen takes their daughter, Mora, to the Statue of Liberty where she meets with her friends, Polly and Chrissie, who tell her about Fin's flight.
At the airport, Fin warns the crowd of the impending storm, but no one takes it seriously. After leaving April to the hospital for surgery, Fin is able to contact Ellen and tells her to get to Bales Tower Hotel on Manhattan as soon as possible. He agrees to retrieve Martin and Vaughn from the ball game, hiring a cabbie, Ben, in the process. At Citi Field, Skye surprises Fin with a kiss, but Fin explains that he and April are back together. The game is cancelled because of the storm, but when sharks start falling from the sky and killing people, Fin and his group improvise weapons to fight them and get on the subway.
On the ferry ride back to Manhattan, a shark kills Chrissie. The remaining three women flee from the severed head of the Statue of Liberty. Meanwhile, the subway tunnels flood, sending sharks to break into the train's rear cabin and kill Brian. Ben, who anticipated Fin's escape, takes Fin and the others to shops in search of weapons and items to make explosives. When the taxi is caught in a flood Fin fashions a rope swing to take Skye, Vaughn, and Martin to safety. When Ben is killed in his attempt and the rope falls away, Fin uses the top of the sharks as stepping stones to reach the others.
Two sharknadoes are converging into a more powerful storm directly above the hotel. Fin and Skye head to the roof to try to bomb the sharknadoes. Polly is flattened by a whale shark, but Ellen and Mora reach the hotel and reunite with Martin and Vaughn. Fin and Skye sling bombs into the tornadoes, but as the storm system is too cold; only a few sharks are knocked down and they are forced to flee down a fire exit stairwell. They meet the Brodys, who were fleeing up the stairwell that is flooding with sharks. They break down a door to escape the stairwell and get out of the building.
April flees the hospital, taking a fire truck to meet Fin and the others. At the Empire State Building a third tornado is expected to merge with the other two. Fin plans to detonate a tank of Freon at the top of the building by connecting it to the structure's lightning rod to freeze the storm. He rallies a crowd of New Yorkers, including the mayor and his task force, to fight the sharks. As he and Skye implement the plan, April, who has affixed a circular saw to her stump, arrives and saves Fin from a falling shark. Skye sacrifices herself to help connect the cables; the Freon explosion throws them in the air where sharks rip Skye in half. While in the twister, Fin grabs onto and rides a great white shark using chains, eventually impaling it on the building's antenna. He reunites with April and finds her lost arm in one of the fallen sharks, using the handgun to kill another one. He then takes the wedding ring from April's severed hand and uses it to propose remarriage, and she accepts.
In a post-credit scene, Fin eats a slice of pizza.