In 1914, aliens known as Mondoshawans arrive at an ancient Egyptian temple to collect the only weapon capable of defeating a Great Evil that appears every 5,000 years. It consists of four stones, representing the four classical elements, and a sarcophagus containing a fifth element in the form of a human, which combines the power of the other four elements into a Divine Light capable of defeating the evil. The Mondoshawans promise their contact, a priest, that they will return with the element stones in time to stop the Great Evil, which will return in three centuries.
In 2263, the Great Evil appears in space in the form of a giant ball of black fire and destroys an attacking Earth spaceship. The current Mondoshawan contact, priest Vito Cornelius (Ian Holm), informs the President of Earth (Tom Lister, Jr.) of the history of the Great Evil and the weapon that can stop it. As the Mondoshawans return to Earth they are ambushed by Mangalores, a race hired by the industrialist Jean-Baptiste Emanuel Zorg (Gary Oldman), who has been instructed by the Great Evil to acquire the stones.
The Mondoshawan's spacecraft is destroyed, though the stones are not onboard; the only item to be recovered is a hand of the fifth element. Scientists take it to a New York City laboratory and use it to re-construct a humanoid woman known as Leeloo (Milla Jovovich). Terrified of her unfamiliar surroundings, she escapes confinement and jumps off a ledge to land in the flying taxicab of Korben Dallas (Bruce Willis), a divorcee and former major in the special forces.
Dallas delivers Leeloo to Cornelius and his apprentice, David (Charlie Creed-Miles), whereupon Cornelius learns that the Mondoshawans entrusted the four element stones to the alien Diva Plavalaguna (Maïwenn Le Besco), an opera singer. Zorg kills the Mangalores because of their failure to obtain the stones, but their compatriots determine to seize them for themselves. Upon learning from the Mondoshawans that the stones are in Plavalaguna's possession, General Munro (Brion James), Dallas' former superior, re-enlists Dallas and orders him to travel undercover, as a rigged radio contest winner, to meet Plavalaguna on a luxury cruise. The publicity surrounding the contest attracts the Mangalores and Zorg. Dallas takes Leeloo with him, while Cornelius instructs David to prepare the ancient temple designed to house the stones, before stowing away on the space plane transporting Dallas to the cruise liner.
Plavalaguna is killed when the Mangalores attack the ship, but Dallas succeeds in retrieving the stones. During the struggle with the Mangalores he kills their leader. After shooting and seriously wounding Leeloo, Zorg finds a carrying case that he assumes contains the stones, which he takes back to his spacecraft, leaving behind a time bomb that forces the liner's occupants to evacuate. Discovering the case to be empty, Zorg returns to the ship and deactivates his bomb, but a dying Mangalore sets off his own device, destroying the ship and killing Zorg. Dallas, Cornelius, Leeloo, and talk-show host Ruby Rhod (Chris Tucker) escape with the stones aboard Zorg's spacecraft.
The four return to the weapon chamber at the Egyptian temple as the Great Evil approaches. They activate the stones, but Leeloo has become disenchanted with humanity and refuses to release the Divine Light. Dallas confesses his love for Leeloo and kisses her. In response, Leeloo combines the power of the stones and releases the Divine Light, causing the Great Evil to become dormant as a new moon in Earth's orbit.
Earth scientists assure the president that the Great Evil is dead. Dallas and Leeloo are placed together in a healing tank to recuperate. When the President arrives and demands to see them, the scientists express reluctance, as Dallas and Leeloo have begun consummating their love.