His earliest prominent appearance in Peruvian history began with his participation in a commanding role of the army of the Libertadores that helped Peru become an independent nation.

When San Martin resigned as "Protector of Peru", Castilla sided with José de la Riva Agüero, who in turn shortly became president in 1823.

Soon after, Castilla, along with Domingo Nieto, overthrew Manuel Ignacio de Vivanco during the Battle of Carmen Alto.

After defeating the other caudillos around the country, Castilla reinstated Menéndez as president, in order to achieve a constitutional transition to democracy.

Important urban projects began during this period, too, such as the first railroad from Lima to Callao, which helped in the transportation of guano from the production centers ready to be shipped abroad.

In 1854, however, another rebellion was led in Peru's second-largest city, Arequipa, by Castilla himself, who was largely urged by other Peruvian liberals to help in the suppression of slavery in the country.

During his absence, the historic Battle of Callao took place, which became Spain's final and unsuccessful move to reconquer independent Peru.

In a last effort to regain power for a fifth time, Castilla – now nearly seventy – and a group of followers landed in Pisagua and proceeded towards the Tiviliche desert.