Osorio de Escobar y Llamas held the offices of canon, inquisitor and vicar-general in the diocese of Toledo.

On 2 August 1655, he was chosen during the papacy of Pope Alexander VII as bishop of Puebla, on the recommendation of Cardinal Moscoso.

There he built the convent of La Santísima Trinidad, hastened the construction of the cathedral, and paid for the chapel and altar of Nuestra Señora de Guadalupe.

He was named to the position to replace Viceroy Juan Francisco Leiva y de la Cerda, who was ordered back to Spain because of corruption.

He was a stranger to profane affairs, and resigned as viceroy at the first opportunity in order to return to his diocese in Puebla.