The Battle of Mbororé, which occurred on 11 March 1641, was a conflict between the Guaraníes inhabiting the Jesuit Missions and the bandeirantes, Portuguese explorers and slavers based in São Paulo.

This was a heavy blow to the Portuguese Empire, which needed slave labor to cultivate sugar and raise livestock, the industries which prevailed on the Atlantic coast of Brazil.

These exploration and slave hunting groups, called bandeiras, were organized and managed as a business for the leading sectors of São Paulo, and their ranks included Mamluks (Portuguese/Indian Mestizos), indigenous Tupi and Dutch who came to Brazil to try their luck.

Between 1628 and 1631 the bandeirantes' leaders, Raposo Tavares and Manuel Antonio Pires Preto and their men periodically struck Guayrá, capturing thousands of Guarani who were then auctioned off at São Paulo.

In 1638, priests Antonio Ruiz de Montoya and Francisco Diaz Tano traveled to Spain in order to report to the King Felipe IV recent events in the missions.

The priests returned to Lima, with the intent of providing weapons to the natives, while Father Tano went to Rome to inform the Pope of the slave-hunting missions in order to obtain a papal protection.

Meanwhile, prior to the imminent danger of the frontiersmen crossing the Uruguay River, the regional priest Diego de Boroa, with the consent of the Governor of Asuncion and Real Audiencia of Charcas, decided that the mission troops should receive firearms and begin military training.

In late 1638, Father Diego de Alfaro crossed the Uruguay River with a number of Guaraní, armed and trained, with the intention of recovering indigenous territory and eventually face the bandeirantes who roamed the region.