In 1839, off the coast of Cuba, a group of Mende tribesmen led by Cinqué rebel aboard the Spanish slave ship La Amistad. They forcibly take control, hoping to navigate back to Africa but are eventually deceived and captured by the U.S. Navy. The ship and its occupants are taken to America, where the Africans are imprisoned, marking the start of a complex legal battle over their fate. Various parties, including the Spanish government and the ship's original owners, claim ownership of the Africans and demand their return.

When the case reaches trial in a New England court, it becomes a symbol of the divisive issue of slavery in America. A passionate young lawyer, Roger Baldwin, takes up the case for the defense, arguing for the freedom of the Mende on the grounds that they were illegally enslaved. As public interest grows, former President John Quincy Adams lends his support, contending that the trial transcends mere property disputes and touches on fundamental human rights. The courtroom drama propels the nation into a heated debate over justice, morality, and human dignity.