When Juan de Salcedo came to Vigan, he renamed the town to Villa Fernandina in honor of the young son of King Philip II. Upon the orders of Salcedo in 1574, the first temporary church of Vigan was built out of wood and thatch. With Salcedo is Augustinian priest Alonso de Alvarado who first attempted to Christianize the Ilocos region.[3] The need to construct a permanent church and convent in Vigan was decided by the Augustinian Chapter on April 30, 1575. It became the first parish in Northern Luzon. The plans to construct the church failed since in 1577, the Augustinians vacated Ilocos. The Franciscans then came to Ilocos with Father Sebastian de Baesa as priest of Vigan. In 1591, the supervision was transferred to the secular clergy. Father Gabriel dela Cruz became the first secular priest of Vigan until 1598. When the Augustinians returned to Ilocos in 1586, they also handled Vigan alternately with the secular clergy. On February 14, 1622, Vigan was officially transferred from the Augustinians to the secular.

The first church was built in 1641 and was damaged by earthquake in 1619 and 1627. A third church was burned in 1739. Upon the request of then Bishop Juan de la Fuente Yepes, the seat of the Diocese of Nueva Segovia was transferred from Lal-lo, Cagayan to Ciudad Fernandina de Vigan (present-day Vigan) through a ceremonial procession on September 7, 1758. With the transfer of the seat of the Diocese, the church of Vigan became a cathedral on that same year. Governor General Jose de Basco ordered the establishment of a new church in 1786. The fourth and present-day church was built from 1790 to 1800 under the Augustinians. It was occupied by the revolutionists under Colonel Juan Villamor in 1896 and by the American forces under Lieutenant Colonel James Parker in 1899.

On July 27, 2022, the church was damaged by the 7.0 magnitude earthquake that hit parts of Luzon. 3 hours after the earthquake, the Cathedral's rector and parish priest Msgr. Gary Noel S. Formoso announced its temporary closure through the Cathedral's official Facebook page, with its reopening upon the advice from structural engineers on its safety for future use. A week after the earthquake, the Vigan City LGU began implementing a color coding scheme that will assess the structural integrity and safety of the city's buildings; due to extensive damage, both the Cathedral and the adjacent Vigan City Bell Tower were placed under the highest level of "Code Red": the affected structures were closed and cordoned off, all functions and activities within were temporarily ceased, and the surrounding areas were placed off-limits to the general public.