In 1561, Aguirre led a mutiny against the expedition's commander, Pedro de Orsúa, and declared his intent to return to Peru and overthrow Spain's colonial government.

In the years since then he has been treated by historians as a symbol of cruelty and treachery in the early history of colonial Spanish America,[3][4] and has become an antihero in literature, cinema and other arts.

[10] In 1544, Aguirre was at the side of Peru's first viceroy, Blasco Núñez Vela, who had arrived from Spain with orders to implement the New Laws, suppress the Encomiendas, and liberate the natives from slavery.

Aguirre took part in the plot with Melchor Verdugo to free the viceroy, who had been imprisoned on the island of San Lorenzo, and turned against Gonzalo Pizarro, the leader of the anti-viceroy/New Laws faction.

In the meantime, thanks to the oidor Alvarez, the viceroy had escaped to Tumbes and gathered a small military force in the belief that all the country would rise up to defend the Crown under the royal flag.

In 1554, needing to put down the rebellion of Hernández Girón, Alonso de Alvarado secured a pardon for everyone who had been affiliated with Aguirre and enlisted in his army.

Aguirre fought and was wounded by two musket shots at the Battle of Chuquingua against Girón, resulting in an incurable limp that caused his peers to ostracise him.

[25] Together with his daughter Elvira, Aguirre joined the 1560 expedition of Pedro de Ursúa down the Marañón and Amazon Rivers with 300 Spaniards and hundreds of natives.

On 23 March 1561, Aguirre urged 186 officers and soldiers to sign a statement acknowledging him as "Prince of Peru, Tierra Firme and Chile".

In Mérida and El Tocuyo several of his soldiers were brought to trial, found guilty of the crimes committed and sentenced to death by dismemberment.