Its present parish priest is Pablo Virgilio Cardinal David, the Bishop of Kalookan, and its rector is Jeronimo Maria J. Cruz.

The parish started as a small visita (chapel-of-ease) initiated by Manuel Vaquero, assistant priest of Tondo, Manila, who with the cooperation of the people also built a place of worship in one of the districts of Caloocan called Libis Aromahan (Sitio de Espinas) in 1765.

During the Philippine revolution against the Spaniards and later, against the Americans, San Roque Church served as the meeting place of the Katipuneros coming from the west coast of Manila going to Balintawak.

In 1900, American general Arthur MacArthur, Jr. invaded Caloocan and the church of San Roque was made caballeriza by the regiment of Col. Frederick Funston.

Pope John Paul II, in his apostolic letter "Quoniam Quaelibet" of June 28, 2003, created the new Diocese of Kalookan, consisting of south Caloocan, Malabon and Navotas (CAMANA Area), and elevated the church to a cathedral.

On December 12, 2015, the faithful of Caloocan witnessed the Solemn Rite of the Dedication of the San Roque Cathedral as the newly renovated altar-sanctuary has been finally completed.

On December 11, 2015, a relic from the bone of San Roque was brought out for public veneration in a vigil in preparation for the dedication of the cathedral.