“The Mission” takes place in South America in the 18th century. Two great colonial forces are competing for the hearts and minds of the native Indians. On the one hand, there are the imperialist plunderers, who want to establish a trade in riches and slaves. On the other hand, there are the missionaries, who want to convert the Indians to Christ.

The central figure in the movie is Mendoza (Robert De Niro), who begins as the first kind of imperialist and ends as the second. Early in the film, he is a slave trader, a man of the flesh. But after he kills his brother in a flash of anger, he yearns for redemption, and he gets it from the missionaries who assign him an agonizing penance: He must climb a cliff near a steep waterfall, dragging behind him a net filled with a heavy weight of armor. Again and again, De Niro strives to scale the dangerous height, until finally all of the anger and sin is drained from him and he becomes a missionary at a settlement run by Gabriel (Jeremy Irons).

The movie now develops its story through the device of letters that explain what happened to the mission settlement. The missionaries dream of a society in which Christian natives will live in harmony with the Spanish and Portuguese. But the colonial governors find this vision dangerous; they would rather enslave the Indians than convert them, and they issue orders for the mission to be destroyed. Irons and De Niro disagree on how to meet this threat: Irons believes in prayer and passive resistance, and De Niro believes in armed rebellion.

In the end, neither approach is effective.