In the mid-19th century, Presbyterians in the Bay Area were determined to establish Presbyterian institutions of learning in the West. In 1871, San Francisco Theological Seminary began when the Synod of the Pacific, a council within the Presbyterian Church, charged a newly appointed Board of Directors with “organizing a theological seminary such as the present wants and future interests of this coast demand.” Four professors and four students first met for instruction at the Presbyterian City College in what now is Union Square on Nov. 14, 1871. Six years later, the Seminary moved to its own building at 121 Haight Street in San Francisco.

By the late 1880s, the Board of Directors was persuaded, chiefly by Arthur Crosby of First Presbyterian Church of San Rafael, to consider moving to a site in Marin County, where the Seminary might serve as the “theological sanitarium of the Church.”

In 1890, with Synod approval, the Board voted to accept the offer of a 14-acre hilltop site in San Anselmo from Arthur W. Foster, seminary trustee, and original instructor William Anderson Scott's son-in-law. The pioneer financier and philanthropist Alexander Montgomery donated the money for student and faculty housing, and the well-stocked library. Montgomery’s gifts to the Seminary eventually totaled nearly a half-million dollars. On September 21, 1892, with 1,200 people in attendance, a faculty of six, and about 20 students, Montgomery and Scott Halls were dedicated and the San Anselmo campus officially opened.

"Its climate is as nearly perfect as possible. An unlimited supply of clean pure water is just at hand. ... There are unlimited and varied opportunities for outdoor exercise." —Arthur Crosby, SFTS director, 1889

In 1900 a new charter gave the Seminary power to grant degrees, and in 1913 jurisdiction over the Seminary was transferred from the Synod to the General Assembly of the Presbyterian Church. Enrollment increased and in 1922, with 106 students, SFTS ranked third in size among Presbyterian seminaries. From its early days, students came from around the Pacific Rim and graduates went into missions abroad. One-third of students in 1922 were women, mostly as special or mission course students.

In the post-World War II era, the Seminary enjoyed unprecedented expansion, with enrollment increasing to more than 300 and new buildings rising. In 1962, SFTS joined with neighboring theological schools in founding the Graduate Theological Union, a consortium based in Berkeley that provides an institutional framework for interfaith discussion and education.

In 2019, the seminary was embedded in the University of Redlands as part of a new Graduate School of Theology.