He then took part in the resistance to the British invasions of the Río de la Plata, during the Napoleonic Wars and later played an important role in the events of the May Revolution of 1810.

[1] Later, as colonel of a unit of Hussars, Rodríguez organized the militias that menaced a political meeting in April 1811, in an attempt to support Cornelio Saavedra.

[2] Following months of political anarchy resulting from the collapse of the Argentine Constitution of 1819, Rodríguez was named Governor of Buenos Aires Province in September 1820.

He enacted land reform, promoting the use of fallow lands, limited the power of the Church, the police and of the military, restored relations with Northeastern Caudillo Estanislao López, and founded the city of Tandil, the nation's first Natural Sciences Museum the Bank of the Province of Buenos Aires and the University of Buenos Aires, among other public institutions.

Rodríguez returned to Buenos Aires, and later became an opponent of Governor Juan Manuel de Rosas, joining Unitarian League leader José María Paz in an 1841-42 rebellion against the Federalist regime.