During the German occupation of France in World War II, Lieutenant Aldo Raine assembles a special team of Jewish-American soldiers known as "The Basterds." Their mission is simple: to spread fear throughout the Third Reich by scalping and brutally killing Nazis. The Basterds' exploits eventually lead them to team up with a British Royal Marine officer on a mission to take down the leaders of the Third Reich. Their plan involves attending a film premiere in Paris, where the Nazi top brass will be in attendance.

Meanwhile, Shosanna Dreyfus, a Jewish woman who narrowly escaped execution at the hands of Colonel Hans Landa, also known as "The Jew Hunter," runs a cinema in Paris. She has her own personal vendetta against the Nazis. When her cinema is chosen to host the premiere of a propoganda film starring German war hero Frederick Zoller, she sees an opportunity for revenge. Unbeknownst to her, her plot intersects with the Basterds' plans, setting the stage for a violent and dramatic convergence of fates at the movie premiere.