Three British MI6 agents, including one "on loan" to the American government, are killed under mysterious circumstances within 24 hours while monitoring the operations of Dr. Kananga, the dictator of a small Caribbean island called San Monique. One is killed at a meeting of the United Nations. The second is stabbed on a street in New Orleans while observing a restaurant called Fillet of Soul; his body is secreted in the coffin of a passing funeral procession. The third agent is killed on the island of San Monique during a voodoo rites ceremony; the high priest uses a poisonous snake to kill the man.
James Bond is ordered by his boss, M, to investigate the deaths and their connections to Kananga. He is sent to New York City, where the first agent was killed and where Kananga is currently visiting the UN. As soon as Bond arrives in New York City, his driver is killed while taking him to meet Felix Leiter of the CIA and Bond narrowly escapes a potentially fatal car wreck. The driver's killer leads Bond to Mr. Big, a gangster who runs the chain of Fillet of Soul restaurants throughout the United States. It is during his confrontation with Mr. Big that Bond first meets Solitaire, a beautiful virgin tarot expert who has the uncanny ability to see both the future and remote events in the present. Big orders his henchman to kill Bond, who, with the assistance of Felix Leiter, manages to escape unscathed.
Bond follows Kananga to San Monique, where he subsequently meets Rosie Carver, a CIA double agent, who is subsequently murdered after Bond suspects her of working for Kananga. Later he meets the boatman Quarrel, Jr. who takes him to the home of Solitaire. Using a stacked deck of tarot cards only showing "The Lovers", Bond seduces her. Solitaire loses her virginity to Bond and also loses her foresight abilities and is forced into cooperating with Bond to bring down Kananga. Bond escapes the island with Solitaire on Quarrel Jr's boat and heads for Louisiana. When they arrive, Bond escapes Kananga's men in a small craft airport. He meets up with Felix Leiter and the two go to the New Orleans Fillet of Soul. When Leiter leaves their table momentarily, it drops down into the floor, where Mr. Big awaits Bond. Big harshly demands to know if Bond had slept with Solitaire. Bond says that the answer is a secret between himself and Solitaire and he'll only reveal the truth to Kananga himself. Big suddenly pulls prosthetic makeup from his face, revealing that he is actually Kananga.
Kananga explains that he is producing two metric tonnes of heroin on San Monique and is protecting the poppy fields with camouflage and by exploiting locals' fear of voodoo and the occult. Through his alter ego, Mr. Big, Kananga plans to distribute the heroin free of charge on the market, which will drive all the other drug cartels out of business, increase the number of addicts, and give Kananga a monopoly of the heroin market. Using the serial number on Bond's watch, Kananga tests Solitaire's truthsaying powers. She fails but Kananga does not reveal the outcome in front of Bond; after Bond is escorted out of the room, he chastises Solitaire harshly for her betrayal and leaves her in the hands of Baron Samedi to be sacrificed in ritual on San Monique.
Kananga turns Bond over to Tee Hee Johnson, a thug with a mechanical arm, who takes Bond to the Farm, a community in the Louisiana backwoods filled with alligators and crocodiles and housing one of Kanaga's heroin labs. Bond is left on a small island to be food for the gators but he jumps on the backs of the reptiles to reach the shore. He sets the Farm on fire, killing some of Kananga's men. He steals a speedboat leading to a furious chase with Kananga's men in pursuit and the local sheriff, J.W. Pepper, and the Louisiana state police trying to blockade Bond and his pursuers. Bond evades them all and is met by Leiter who informs him that Kananga, Samedi and Solitaire left for San Monique.
Bond goes back to San Monique, ordering Quarrel Jr to plant explosives in the poppy fields. Bond interrupts the voodoo sacrifice, rescuing Solitaire. While Bond holds the ritual attendees at bay, Baron Samedi pops up from a grave. Bond shoots him, finding he's a ceramic decoy, however, the real Samedi appears. Bond fights the man briefly & the villain ends up falling in a coffin full of poisonous snakes, seemingly bitten to death. Bond and Solitaire travel below ground into Kananga's lair. They find Kananga, who tells Bond that his wet suit was found and that the explosives he used on the poppy fields have done too little damage to interrupt production. Bond and Solitaire are lashed to a small crane over a shark pool; Kananga slashes Bond's forearm several times, drawing blood to bait the sharks. Using his magnetic watch, Bond retrieves a gas pellet from his shark gun and cuts the ropes holding him. After a brief fight with Kananga, he forces the gas pellet in Kananga's mouth, rapidly inflating the villain who floats to the top of the room and explodes.
After the job is done, Felix leaves Bond and Solitaire on a train out of the country. Tee Hee makes a last attempt on Bond's life and is ejected from their train compartment at high speed. However Baron Samedi is seen perched on the nose of the speeding train in his voodoo ensemble and laughing heartily.