The church community in San Antonio de Padua of Pila, Laguna, along with the Mission of Lumban, is among the oldest Catholic communities in the province, both established in 1578. Pila holds the distinction of being home to the oldest Antonine Church in the Philippines. Originally situated in Pagalangan (now part of Victoria, Laguna), the church was built using stones that took 18 years to complete and was regarded as the most beautiful church in the province. Due to frequent flooding from the expanding Laguna de Bay in the late 18th century, the town and its church were relocated to its present site by 1801. The old church foundation and belfry remain as historical markers of the original location.

In 2002, Pila's church was elevated to a diocesan shrine by Bishop Francisco C. San Diego. The shrine gained national recognition on January 26, 2019, when it was declared the National Shrine of San Antonio de Padua, a significant achievement spearheaded by Fr. Edwin Lusterio and the shrine promoters. The declaration ceremony took place on April 23, 2019, led by Archbishop Romulo Valles. In 2021, the National Shrine formed a Spiritual Bond of Affinity with the Basilica of St. Anthony in Padova, Italy, through the efforts of Fr. Emil Urriquia, further strengthening its international connection.

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