In the summer of 1839, on a stormy night off the coast of Cuba, 53 Africans held captive in the cramped cargo holds of the Spanish slave ship La Amistad break free of their shackles. Led by Cinque (DJIMON HOUNSOU), they arm themselves, take control of the ship and reclaim their freedom. They have one goal: to return to Africa.

Without the navigational skills to guide them home, the Africans are forced to rely on the two surviving members of the crew. But they are tricked. After two months on a ragged course up the Eastern seaboard, the Amistad is captured by an American naval ship off the coast of Connecticut and the Africans were charged for murder and piracy.