Hawaii, May 1977. After the success of Star Wars, George Lucas and Steven Spielberg meet to find a new project to work on together, the former as producer, the latter as director. The story of how the charismatic archaeologist Indiana Jones was born and how his first adventure, released in 1981, triumphed at box offices around the world.

In the eleventh film in the series, in December 1916, Indy, still stationed in Africa, is promoted to Captain and then ordered to cross the jungle with Remy and Captain Boucher to pick up a shipment of weaponry. Along the way, Ubangan Sergeant Barthélèmy picks up the sole surviving child from a disease-ravaged village despite Boucher's orders against it. On the way back, Indy and company succumb to disease themselves, and are picked up by Albert Schweitzer and the orderlies from his jungle hospital. At first resistant to being treated by a German, Indy soon begins to realize that Schweitzer is not interested in war, only attempting to cure people against all odds.

When fellow operatives and friends disappear during a mission in Hong Kong, Cleopatra Jones comes to help. She discovers the disappearance involves The Dragon Lady, a feared lipstick lesbian who runs a casino and the local drug trade.

A boy rises to the occasion with his best friend (a lovable talking dog) to save his home and family.