He finished his studies in art in 1786, was ordained as a Roman Catholic priest in 1796 and served in several churches around the city.
During this time, he started to sympathize with rebellious issues and for this reason, he was jailed by the Spanish colonial authorities shortly after the war started. He managed to escape from prison and eventually joined the revolutionary army of José María Morelos in December 16 of 1811. One day before the Izucar battle Morelos named him colonel and ordered to create his own forces, with the population of Jantetelco, Matamoros created 2 regiments of cavalry, 2 battalions of infantry and 1 of artillery, in total his forces were composed by 2000 men.
During the Siege of Cuautla from February 9 to May 2 of 1812, Morelos recognized Matamoro's ability in the battlefield and promoted him to the rank of lieutenant general, effectively becoming second on command of the army. One night Matamoros broke the siege and could join Miguel Bravo in Aculco. Once the siege was lifted, the campaign continued in Oaxaca, it was surrounded in November 25 of 1812.
After the battle, on 5 January 1814, the army moved to Puruaran, Agustin de Iturbide attacked the Morelos army and it was a disaster, in the middle of the confusion Matamoros tried to escape crossing the river (close to Puruaran) but was captured by Eusebio Rodríguez, a soldier from the battalion of "Frontera", who received 200 pesos and a promotion. Allegedly Morelos offered 200 Spanish prisoners in exchange for Matamoros, but was turned down by the Spanish colonial authorities. Matamoros was removed from the priesthood and tried for treason.
He was executed by firing squad in Valladolid, Michoacán on February 3, 1814. In 1823, Matamoros was honored as "Benemérito de la Patria". His remains now rest in the Independence Column of Mexico City.
Matamoros is a national hero of Mexico. In his honour, the Cuernavaca International Airport in Cuernavaca, Morelos, is named after him, as well as the cities of Izúcar de Matamoros, Puebla, Matamoros, Coahuila de Zaragoza, and Matamoros, Tamaulipas.