Religion was always part of Army life, and major posts often built chapels staffed by Army chaplains to minister to soldiers and their families. The Chapel of Our Lady was the Presidio’s first house of worship. It was built in 1864 in a simple version of the Victorian Gothic style to serve as a Protestant Episcopal chapel. The first post chaplain was the Rev. Daniel Kendig, an Episcopal minister. It is probable that Kendig, supported by the post's officers and members of the Episcopal Dioceses of California, raised the funds for the construction of the chapel.

Over time, the venerable building became overgrown with ivy and only its square steeple poked up through what appeared to be a topiary mound of greenery. In 1932, a larger Post Chapel (today the Interfaith Center) was built on a slope close to the San Francisco National Cemetery. The Chapel of Our Lady was then consecrated to Roman Catholic services.

Scissor trusses distinguish the chapel’s interior. In 1952, the old chapel was modernized and remodeled by architect Hewlett Wells. The roof, steeple, and board-and-batten siding of the original building remain. The wall behind the altar was replaced with clear windows providing a view of the forest beyond. The west wall facing the side patio garden was replaced with large windows trimmed with stained glass panels that opened the building to its surroundings. In the patio is a wood cross commemorating the dedication of the Presidio with a mass on September 17, 1776.

In 1970, to better serve the active post, the building was expanded again. The nave was extended and the altar was turned around to face the congregation in keeping with the liturgical changes introduced by Vatican Council II. The scissor trusses were decorated with stenciled designs. The result of these changes was to take a small, enclosed, Victorian building and open it up to its surroundings. This small building epitomizes one of the fundamental changes in California architecture after the 1950s: the “opening up” of buildings to patios and gardens.

The chapel and its garden stand on the site of the original Spanish Presidio of 1776 and are located at the head of the Civil War-era parade ground on the Main Post.