Adolfo finished law school and joined the Unitarian army in the civil war. In 1860, after the Battle of Pavón and the National Union Pact, he took part in the commission responsible for the constitution reform of 1860. He was elected a deputy in 1862. When the subject of federalisation, supported by Bartolomé Mitre, was considered in the Chamber of Deputies, Alsina provoked a split in the Partido Unitario and founded the Partido Autonomista.
In 1866 he was elected governor of the Buenos Aires Province. Alsina considered running for president, but withdrew when he discovered he did not have the support of most of the province. Domingo Sarmiento was elected president, and named Alsina his vice-president.
When the presidency of Sarmiento finished in 1874, Alsina joined Nicolás Avellaneda to create the Partido Autonomista Nacional, through which Avellaneda reached the presidency and named Alsina Minister of War and Navy.
At the end of 1875, the Native Americans of Patagonia and the Pampas, especially the Mapuche, launched organised attacks against the territorial expansion of the southern border of the emerging nation'. The first stage of the Conquest of the Desert began with the creation of a two meter deep, three meter wide trench to prevent the free movement of horses and stolen cattle. Alsina also ordered the creation of forts intercommunicated by telegraph.
Trying to understand the native peoples, he decided to study the situation personally, but he fell ill intoxicated while in Carhué, and died of kidney failure.