When Father John O'Sullivan arrived at Mission San Juan Capistrano in 1910, he found a community scattered and buildings crumbling into dust. The original stone church had been destroyed in the 1812 Wrightwood earthquake, leaving only the Serra Chapel standing, the oldest church building in California and the only place where St. Junipero Serra is known to have celebrated Mass. O'Sullivan dedicated his life to rebuilding, restoring the old facilities while nurturing the parish community. He envisioned constructing a new church modeled on the 1806 stone church, but would not live to see his dream realized. He served faithfully until his death in 1933, leaving behind both a restored mission and an unfulfilled vision.

The modern push for a new parish church came in 1976 when Father Paul Martin was named pastor. By then, the Catholic population of the area had grown considerably, and the historic Serra Chapel could no longer accommodate the faithful. Architect John Bartlett designed a church patterned after the original 1806 stone church, though not a replica of it. Joseph Byron Jr. of Alex Sutherland Construction built the structure, while historian Norman Neuerberg designed the interior and painted much of the decorative sacred art that adorns the walls. The church was completed in 1986, funded through pledge drives and donations from mission visitors, finally fulfilling O'Sullivan's vision.

The basilica's most striking feature is its Grand Retablo, a massive altar-backing carved in cedar and covered in gold leaf, reminiscent of 17th and 18th-century Spanish colonial and Mexican colonial retablos. At its focal point sits the Trinity: the crucifix, God the Father depicted as an ancient patriarch, and the Holy Spirit shown as a dove. Beneath them watches Our Lady of Guadalupe. Four saints grace the retablo: Saint Francis of Assisi, patron of the mission's founding Franciscan order; Saint Joseph; Saint Junipero Serra, founder of the mission; and Saint Kateri Tekakwitha, significant to the area's Native American population. The Talleres de Arte Granda in Madrid created this masterwork.

The Mission Basilica is more than a place of worship; it is a center of active ministry. Serra's Pantry, named for the mission's founder, operates as a registered food agency distributing food and hygiene supplies to several hundred local families. The Mission Basilica School educates children from pre-kindergarten through eighth grade, continuing the educational tradition that Spanish missions brought to California. In 2003, the church received the additional designation of national shrine, recognizing its significance not just to California Catholics but to the entire nation. The parish continues to grow, a living testament to the persistence of faith across generations.