In 1938, an art collector appeals to eminent archaeologist Dr. Indiana Jones to embark on a search for the Holy Grail. Indy learns that a medieval historian has vanished while searching for it, and the missing man is his own father, Dr. Henry Jones Sr.. He sets out to rescue his father by following clues in the old man's notebook, which his father had mailed to him before he went missing. Indy arrives in Venice, where he enlists the help of a beautiful academic, Dr. Elsa Schneider, along with Marcus Brody and Sallah. Together they must stop the Nazis from recovering the power of eternal life and taking over the world!

Humble stamp dealer Otto Becker has little to do with international politics, so when he receives a surprise visit from his estranged twin brother and Nazi spy, Baron Hugo von Detner, his world is thrown into turmoil. Threatening Becker with deportation, Hugo forces him to use his shop as a front for espionage.