The film opens with a scroll saying that when Alfred Hitchcock's film The Birds (1963) was released, audiences laughed at the notion of birds revolting against humanity, but when an attack perpetrated by birds occurred in 1975, no one laughed. This is followed by a pre credits sequence of a tomato rising out of a woman's garbage disposal. Her puzzlement turns into terror as the tomato draws her into a corner. Following the credits, the police investigate her death. One officer discovers that the red substance with which she is covered is not blood, but tomato juice.
A series of attacks perpetrated by tomatoes occurs (including a man dying by drinking tomato juice made from a killer tomato, a boy heard being gobbled up by a killer tomato, and a sequence where the tomatoes attack innocent swimmers, in a parody of Jaws). While the President's press secretary Jim Richardson tries to convince the public that no credible threat exists, the President puts together a team of specialists to stop the tomatoes, led by a man named Mason Dixon. Dixon's team includes Sam Smith, a disguise expert who is seen at various points dressed as, among other things, George Washington, Abraham Lincoln, and Adolf Hitler; scuba diver Greg Colburn; Olympic swimmer Gretta Attenbaum; and parachute-toting soldier Wilbur Finletter.
Smith is sent out to infiltrate the tomatoes at a campfire, eventually blowing his cover while eating a hotdog and asking if anyone could "pass the ketchup." Colburn and Gretta are sent to sectors, while Finletter stays with Mason. Meanwhile, the President sends Richardson to the fictitious ad agency Mind Makers, where executive Ted Swan spends huge amounts of money to develop virtually worthless ploys, including a bumper sticker with "STP" for "Stop Tomato Program" on it, a satirical reference to both the real "whip inflation now" campaign with its widely ridiculed "WIN" slogan and STP motor oil decals and bumper stickers which were commonplace in the 1970s. A human is revealed to be also plotting to stop Dixon when a masked assassin attempts to shoot him, but misses. A senate subcommittee meeting is held where one secret pamphlet is leaked to a newspaper editor, who sends Lois Fairchild on the story. While she tails Finletter, he mistakes her for a spy and trashes a hotel room attempting to kill her. He then chases the assassin as the masked man fails again to kill Dixon, but loses him.
Gretta is killed and further regression has led leaders to bring in tanks and soldiers to the West Coast in a battle that leaves the American forces in shambles. Dixon, walking among the rubble, sees a trail of tomato juice and decides to investigate. He ends up being chased by a killer tomato to an apartment where an oblivious child is listening to the radio. The tomato is about to kill Dixon, but suddenly flies out the window. Dixon peers out to see if it has died, and he spots the assassin hijacking his car. He chases the assassin in a "slow car chase" that has since been copied by other comedies. Dixon is eventually knocked out by his own car. Awakening, Dixon finds himself captured by Richardson. Though he did not create the killer tomatoes, he has discovered how to control them and plans to do so once civilization has collapsed - leaving him in control. He is about to reveal his secret of control to Dixon when Finletter charges in and runs him through with his sword. Dixon, picking up some strewn records, realizes that he has seen the tomatoes retreat at the sound of the song "Puberty Love", but had not put two and two together until now. He orders Finletter to gather all remaining people and bring them to the stadium. Finletter remarks that "only crazy people" are left in the nearly deserted city, resulting in a motley assortment of people in costumes facing the attacking tomatoes at the stadium.
The tomatoes are cornered in a stadium. "Puberty Love" is played over the loudspeaker, causing the tomatoes to shrink and allowing the various people at the stadium to squash them by stomping on them repeatedly. Fairchild, meanwhile, is cornered by a giant tomato wearing earmuffs, hence cannot hear the music. Dixon saves her by showing the tomato the sheet music to "Puberty Love". He professes his love to her, in song. The film ends with a carrot that rises from the soil and says, "All right, you guys. They're gone now."
