He began his schooling in Macuspana and completed his studies in Villahermosa (then called San Juan Bautista) at the Instituto Juárez, where he graduated with a teaching degree.
Santamaría would be the only one on Elías Calles's hit list to not fall the night of October 2, 1927, an event known as the "Huitzilac Massacre," which resulted in the summary executions of Serrano and twenty six other generals, and which President Álvaro Obregón ordered out of fear of military rebellion.
After returning to Mexico Santamaría re-entered politics by joining the Institutional Revolutionary Party (PRI); eventually going on to serve as a Senator of the Republic for Tabasco from 1940 to 1946.
Immediately after the conclusion of his term he was selected by the party as its candidate for the governorship of Tabasco, competed against three opponents and won handily, reportedly receiving 95% of the votes.
As governor he worked to improve his state's educational system and general level of cultural and technological development, while continuing to write books and essays on a variety of subjects.