During the time of the Constitutional Congress of 1824, Quiroga led its forces through the Andean provinces to oppose the centralist tendencies of President Bernardino Rivadavia and the officers of the National Army, which were carrying away a compulsory levy for the upcoming Cisplatine War (1825–1827).

He overthrew the centralist governor of San Juan shortly after the central government signed a series of treatises with Great Britain by which religious freedom was enforced and La Rioja mines were given in usufruct to British enterprises.

A devout catholic who would quote the Bible from memory, Quiroga considered Rivadavia a "persecutor of the Church" and joined federalist rebels who would later overthrow the national government.

[1] After the Cisplatine war, the officers of the returning army (of centralist tendencies, known as unitarios) deposed the federalist governments in an attempt to restore the centralised rule of Buenos Aires.

Quiroga decided not to give up and tried a more ambitious attempt, marching through territories still occupied by native aboriginals, in order to bypass Córdoba, and attack directly Mendoza, where it succeeded.

For most of the first years as a powerful caudillo, Facundo Quiroga had very little to say about his own personal religion, hoping to stay out of the conflict over control of the masses between Catholicism and the emerging Argentine government.

Rosas, as the Confederation leader, led the criminal investigation that ended with the prosecution of the governor of Córdoba, José Vicente Reinafé, and his brother as the intellectual perpetrators of the crime.

Instead, Ariel De La Fuente states in his 2000 book, Children of Facundo, that he: "accumulated his fortune during eighteen years of married life, a period that coincides, almost exactly, with his entire political career (1818-1835).".