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 unit. Her puzzlement turns into terror as the tomato draws her into a corner. Following the opening credits, the police investigate her death. One officer discovers that the red substance she is covered with is not blood, but tomato juice.
A series of attacks perpetrated by tomatoes occur (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 bay area of San Diego, in a parody of 'Jaws').
While the President's press secretary, Jim Richardson, tries to convince the public that there is no credible threat, the president puts together a team of specialists to stop the tomatoes led by a Euro-American man named Mason Dixon. Dixon's team includes Sam Smith, an African-American disguise expert who is seen at various points dressed as, among other things, George Washington, Abraham Lincoln and Adolf Hitler; Euro-American Navy diver Greg Colburn; Central-Russo Russian Olympic swimmer Gretta Attenbaum; and Euro-American parachute-toting soldier Wilbur Finletter.
Smith is sent out to infiltrate the tomatoes at a campfire, eventually blowing his cover while eating a hamburger 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 the real "whip inflation now" campaign and its widely ridiculed "WIN" slogan. It is revealed that a human is 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 reporter 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 when he spots the assassin hijacking his car. He chases the assassin on foot until he is knocked out when it is revealed that Richardson is behind the tomatoes. He is about to reveal his secret of control when Finletter charges in and runs him through. Dixon, picking up some strewn records, realizes that both times the tomatoes left him the new hit song "Puberty Love" had been on the radio. He orders Finletter to gather all remaining people and bring them to the stadium, which is soon attacked by the tomatoes.
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. 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 Earth and says "All right, you guys. They're gone now."
The end credits title card appears which is a joke to stay tuned for the sequel, "Attack of the Killer Carrots".