Manuel was born in São Miguel Island, he arrived at the Rio de la Plata in the company of their parents Amador Vaz de Alpoim and Margarida Cabral de Melo, belonging to the Portuguese nobility. His family had lived for five years in the Portuguese colony of Brazil, in which they had taken refuge after the earthquake in the Azores islands, in 1591.
He began his studies in Buenos Aires, to continue his education at Lisbon (Portugal). In 1613, he returned to Buenos Aires, and began to work in his father's business.
During 1620s and 1630s, Manuel Cabral de Melo e Alpoim occupied several government posts, including the positions of alcalde, regidor and Maestre de Campo. Resident in Corrientes was appointed as Lieutenant Governor of Province in 1625. He led the crackdown against the rebel Indians, who in 1628, had murdered the Spanish Jesuits among them Roque González de Santa Cruz, cowardly attacked by the cacique Ñezú in reduction of San Nicolás, located across the Uruguay River. Commanding an army of 200 soldiers of Guarani origin, departed from the city of Itatí to Rio Grande do Sul, in support of the Jesuits. The rapid intervention of Alpoim, saved the lives of hundreds of people. Also gave approximately 40.000 cattle for creating stays in the area.
The heart of Roque González de Santa Cruz, burned and pierced with an arrow, was found by Alpoim inside a bag of relics. His heart wrapped in the blanket, was escorted by soldiers of Captain Alpoim to the city of Corrientes.
With large effort was also devoted to livestock, in 1620s, he had obtained permission for the exploitation of "ganado cimarron" (wild cattle and horses). He had a ranch in Monte Grande, and also ran his mother's ranch in Luján.