St. John’s University is a missionary university established in Shanghai by the Episcopal Church in the United States in 1879 and existed for 73 years. It is the oldest missionary institution for higher education in Shanghai.

St. John's University School of Medicine originated from the Medical Department established by Henry William Boone in Tongren Hospital of Hongkou District in 1880. In 1896, St. John’s College was reorganized and set up a medical department with Henry as the director. Students in Tongren Hospital were moved to the department. The schooling duration was four years. In 1906, St. John’s College registered in the United States as St. John’s University, and the schooling system was changed to seven years. Medical students were conferred a doctoral degree upon graduation. In 1914, Guangzhou Medical College of Pennsylvania was merged into St. John’s University Medical School with the latter’s name adopted for the new school. In 1947, St. John's University School of Medicine was established and Ni Baochun became the dean. In 1949, there were 59 teachers, 298 students at school, and 25 graduates that year. The teaching hospital was Tongren Hospital equipped with 400 beds.

St. John’s University School of Medicine started early with a long schooling system, focusing on the quality rather than the number of graduates. A total of 466 students were fostered there. Many were outstanding medicine practitioners or experts. In September 1952, St. John’s University was abolished as faculties of colleges and universities across the country were adjusted. St. John's University School of Medicine merged with Aurora University School of Medicine and Tongde Medical College to form Shanghai Second Medical College.