The Treaty of Madrid in 1750 transferred sovereignty over the area from Spain to Portugal. The Spanish Jesuit missions were ordered to move to the retained Spanish territory west of the Uruguay River. The Guaraní tribes refused to comply with the order to relocate from their homelands, now deemed in Portuguese "territory." This led to the Guarani War. A joint Portuguese-Spanish army attacked and defeated the Guaraní, and the mission was closed.
The cathedral (Catedral Angelopolitana), built in the 1920s in nearby Santo Ângelo city, is modeled after that at the São Miguel das Missões reduction.
Old church bell and native art in the Missions Museum, São Miguel das Missões.
The Mission (1986) — film starring Robert De Niro and Jeremy Irons, about the Jesuit Missions of the Guaraní and Guaraní War. The film set represented what is known of the appearance of the 18th-century São Miguel das Missões.