He occupied diverse posts in government, and had a successful civil career as an advocate and professor of law at the University of Buenos Aires.

Under the government of Juan Manuel de Rosas, he had to leave the country, as his liberal ideas did not please the dictator at all.

When Rosas was deposed by Justo José de Urquiza, Alsina returned to Buenos Aires, and he was elected provincial Governor in 1852.

In 1859, open hostilities broke out between Buenos Aires and the Argentine Confederation, led by Urquiza.

When Bartolomé Mitre (President of Argentina between 1862 and 1868) offered him a position as member of the Argentine Supreme Court he refused and remained serving as a Senator until his death, which occurred just a few months after he took the oath of his son Adolfo Alsina, who became Vice President of Argentina in 1868.