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. The weapon consists of four stones, containing the essences of 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 into a divine light capable of defeating the evil. The Mondoshawans promise their human contact, a priest from a secret order, that they will come back with the weapon in time to stop the great evil when it returns.

In 2263, ^[b] the great evil appears in deep space in the form of a giant ball of black fire, and destroys an attacking Earth spaceship. The Mondoshawans' current contact on Earth, priest Vito Cornelius, informs the President of the Federated Territories about 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, who has been directed by the great evil to acquire the element stones.

The Mondoshawans' spacecraft is destroyed, and the only "survivor" is a severed hand in a metal glove from the Fifth Element's sarcophagus that still contains some living cells. Human scientists take it to a New York City laboratory where they use it to reconstruct a powerful humanoid woman who takes the name Leeloo. Terrified of the unfamiliar surroundings, she breaks out of confinement and jumps off a high ledge, crashing into the flying taxicab of Korben Dallas, a former major in the special forces.

Dallas delivers Leeloo to Cornelius and his apprentice, David, and it is revealed that she is the Fifth Element. As Leeloo acclimates to Earth and prepares to seek out the element stones, Cornelius learns from her that the stones were not on the Mondoshawans' ship, but were entrusted to an alien opera singer, the diva Plavalaguna. Zorg kills many of the Mangalores for their failure to obtain the stones, but the survivors are determined to seize the artifacts in revenge. Learning from the Mondoshawans that the stones are in Plavalaguna's possession, General Munro, Dallas' former superior, recommissions Dallas and orders him to travel undercover to the planet Fhloston to meet Plavalaguna in a flying luxury hotel where she is performing a benefit concert; a radio contest awarding a Fhloston vacation, sponsored by flamboyant talk show host Ruby Rhod, is rigged to secure Dallas' passage. Dallas takes Leeloo with him after learning she and Cornelius are on the same mission he is. Meanwhile, Cornelius instructs David to prepare the temple designed to house the stones, then stows away on the spacecraft transporting Dallas, Leeloo, Rhod and his entourage to the cruise liner.

Plavalaguna is killed when the Mangalores attack the hotel during her concert, but Dallas succeeds in retrieving the stones from the dying diva. During his struggle with the Mangalores, he kills their leader, rendering the remaining Mangalores unwilling to continue fighting. Meanwhile, Zorg arrives, shooting and seriously wounding Leeloo before taking a carrying case that he presumes contains the stones back to his spacecraft. He leaves behind a time bomb that forces the hotel's occupants to evacuate. Discovering the case to be empty, Zorg returns to the hotel and deactivates his bomb, but a dying Mangalore sets off his own device, destroying the hotel and killing Zorg. Dallas, Cornelius, Leeloo and Rhod escape with the stones aboard Zorg's spacecraft.