In mid-eighteenth-century South America, Father Gabriel, a Spanish Jesuit priest, gains the trust of the Guarani indigenous community and establishes a mission in their jungle territory at the border between Argentina and Paraguay. Meanwhile, Captain Rodrigo Mendoza, a mercenary soldier and slave trader who preys on indigenous people, kills his half-brother, Felipe, over the love of a woman. Mendoza is spared punishment but falls into a deep depression. Father Gabriel meets with him and encourages him to atone for his sins by dragging a heavy load, including his armor and sword, through the jungle to his mission. Once there, Mendoza is forgiven by the Guaranis, and his penance is done. Moved by the educational and spiritual environment of the mission, Mendoza vows to stay and help out. He eventually becomes a Jesuit under the guidance of Father Gabriel and fellow priest Father Fielding. The mission is threatened when a new treaty between the Spanish and the Portuguese reapportions some Spanish land to Portugal, including the Guarani territory. As the Portuguese condone slavery, the Guaranis are now subject to be sold. Cardinal Altamirano, an emissary of the Pope, travels from the Vatican City to Father Gabriel’s mission, to determine its fate. Altamirano faces a difficult decision, since siding with the Jesuits might result in a fractured European Catholic church and condemnation by the Portuguese. Altamirano announces the closing of the mission and tells the Guarani it is God’s will that they leave. The Guarani reject the notion, as do Father Gabriel and Mendoza. Although Father Gabriel does not condone violence, Mendoza insists that military measures must be taken to defend the mission. Mendoza trains the Guarani to fight against Portuguese attack. A joint Spanish-Portuguese invasion ensues. Mendoza is shot and killed, and Father Fielding dies in the act of killing the Portuguese commander. The invaders broach the mission village and are momentarily awed by the holy atmosphere. The Spanish commander orders his men to continue, and Father Gabriel is killed, along with the remaining priests and the majority of the mission’s inhabitants. Only a small group of Guarani flee into the jungle. While Portuguese leader Hontar is satisfied that the necessary action was carried out, Altamirano laments his role in the massacre. Soon after, surviving Guarani children travel back to the site to retrieve their belongings. They fill their canoe and travel upriver, already haunted by the memory of the mission.