Enrile, originally known as Cabug, was once a barrio of Tuguegarao. In September, 1849, it was established as a separate town and named in honor of Governor General Pascual Enrile, who was responsible for the construction of roads in Northern Luzon. Also on this day, the Dominicans gave Enrile her first priest in the person of Fray Concha. He was supposed to build Enrile a church but it turned out to be Fray Pedro Alcantara, O.P. who started the construction. However, the sporadic activities of the nucleus of the Revolution hampered its completion. It was only late in 1877 when Fray Francisco Bueno, O.P. and Atty. Vicente Guzman completed the church.

When the Revolution broke out in 1898, priests, nuns and Spanish gentlemen from different parts of the province attempted to elude captivity in Enrile. For months they covered in the safe chambers of the church. Although in the end they were all captured but spared from harm by Don Vicente Guzman who had become a respected nationalist.

General Emilio Aguinaldo was in Enrile when he retreated from the American Forces. He was later captured by the Americans in Palanan, Isabela. (General Aguinaldo revisited Enrile on May 8, 1940).