[4] In the 1880s, the church's third Rector was involved in founding the Mission District's St. Luke's Hospital, at the time the only San-Francisco medical institution to treat the Chinese community.

In the 1890s, the church erected a granite neo-Byzantine basilica, which was dynamited in 1906 to form a firebreak during the great San Francisco earthquake and fire.

Albert O. Lott, hosting progressive theatre by the Pitschel Players, the "Wednesday Night Fights" in which the vestry engaged with the community on topics of contemporary interest, and various public events, including the wedding of Country Joe McDonald, which was featured on the cover of the 1968 Together album by Country Joe and the Fish.

There was also an outpouring of musical creativity, notably original works written and produced by the then-choirmaster Jeff Davis, the carillonist for the Berkeley, California carillon.

In the 1970s, in reaction to the continuing deterioration of the neighborhood around the church caused by the erection of 1950's housing projects, rector Winston Ching founded St. John's Educational Thresholds Center, a tutoring program for mission youth.