Nazisterne slagtede Shosannas familie. Nu står hun i centrum for en storstilet hævnaktion. Takket være en glamourøs filmstjerne, der har bånd til modstandsbevægelsen, er premieren på tyskernes seneste nationalromantiske bjergfilm henlagt til Shosannas biograf i Paris. På gæstelisten står såvel Hitler som hendes banemand, den belevne major Landa, samt en jødisk bataljon af barske skalpejægere, Inglourious Basterds.
The film revolves around a local street-racer who partners with a rich and arrogant business associate, only to find himself framed by his colleague and sent to prison. After he gets out, he joins a New York-to-Los Angeles race to get revenge. But when the ex-partner learns of the scheme, he puts a massive bounty on the racer’s head, forcing him to run a cross-country gauntlet of illegal racers in all manner of supercharged vehicles.