Upon the death of his father, Cánovas came to Madrid to live under the protection of his relative, the writer Serafín Estébanez Calderón (Estébanez Calderón, Serafín), and of the banker José Salamanca. In 1852 he was introduced to General Leopoldo O'Donnell (O'Donnell, Leopoldo, Duque De Tetuán), whose political mentor he later became. His first political act was his involvement in the conspiracy of O'Donnell (1854), the program for which (Manifesto of Manzanares) was the work of Cánovas. In the 1854 elections Cánovas was elected to the Cortes (parliament) for the district of Málaga, but his unwillingness to support the Baldomero Espartero (Espartero, Baldomero, príncipe de Vergara)–O'Donnell government led him to resign and accept the lucrative position the government offered him in the Vatican (1855).

After his return from Italy in 1857, Cánovas held several governmental posts until he became minister of the interior in the administration of Alejandro Mon in 1864 and of colonies under O'Donnell the following year. He participated in the Cortes convened by General Juan Prim (Prim, Juan) in 1868 after the dethronement of Isabella II on September 29 but refused to support the monarchy of Amadeus (1870–73). Instead, Cánovas became the leader of the Alfonsines and prepared the return of Alfonso XII. After the proclamation of the king by General Arsenio Martínez Campos (Martínez Campos, Arsenio) at Sagunto on December 29, 1874, Cánovas became prime minister, a post in which he alternated with Práxedes Mateo Sagasta (Sagasta, Práxedes Mateo), leader of the liberal party. When King Alfonso XII died on November 25, 1885, Cánovas secured the peaceful transmission of power to Queen María Cristina (María Cristina De Habsburgo-Lorena) and the future accession to the throne of Alfonso XIII by the so-called Pact of Pardo with Sagasta and Martínez Campos and by his own resignation as prime minister.

His domestic policy brought to Spain public order and a degree of national unity, but he did not satisfy the working class. In the question of Cuba, Cánovas committed himself to a war policy and failed to give Cuba any liberal reforms. Furthermore, Cánovas aggravated the situation by sending to the island, after the resignation of Martínez Campos, General Valeriano Weyler y Nicolau (Weyler y Nicolau, Valeriano, Marqués De Tenerife), whose repressive measures did not promote the cause of Spain before the eyes of the U.S. government. He was still trying to solve the Cuba problem when he was assassinated by an Italian anarchist.

Cánovas del Castillo was a learned man, a member of the academies of language and history. He published numerous historical works.