Mansilla was born in a house in the Montserrat neighborhood, on the corner of Tacuarí and Potosí streets (today Alsina), known in colonial times as "the old prison" on December 23, 1831 (Saint Victoria's Day).

One day he was surprised by his father reading the social contract of Rousseau, which determined that his father, fearing that such readings reach the ears of his uncle Juan Manuel, little affection to those inclinations, decided to send in committee in order to acquire goods on a trip to India, countries of the East and Europe where he knew exotic places for the time like Calcutta and Egypt, ending his trip in London and Paris.

After the overthrow of Rosas, as a consequence of the Battle of Caseros, he undertook another trip to Europe, accompanied by his father and brother Lucio Norberto, who shared part of the journey to Brazil with Sarmiento.

Around 1856, he gained an interest in journalism, but an incident in a theater occurred, where he insulted Senator José Mármol loudly, challenging him to a duel for an injury inflicted on his family in the novel Amalia.

Appointed commander of the southern borders of Córdoba, he devoted himself to meticulously exploring the area between the Cuarto and Quinto rivers, as a result drawing a detailed topographic map.

As a result of this experience, he wrote a series of letters, first published in the Buenos Aires newspaper La Tribuna as a booklet and shortly thereafter edited in book format, an account that constitutes his best-known literary work, An excursion to the ranqueles indians .

On the return of his expedition, which lasted twenty days, in Villa Mercedes, Mansilla found himself suspended from his post because, proceeding without consulting his boss, he had ordered the execution of a recidivist deserter, after a very brief council of war.