St. John's University was one of the most famous church universities. It started as St. John's College. In 1877, Samuel Joseph Schereschensky, bishop of American Episcopal Church, began to prepare the establishment of the college. In 1879, the college was formally opened.

At the beginning, in order to attract students and broaden its influence, the college charged no fees and offered free board and lodging as well as other daily necessities.

Francis Lister Hawks Pott of American Episcopal Church served as the principal of the college from 1880 to 1942.

At the beginning, there were two departments, namely the department of the Chinese language and the department of theology. In 1880, a department of medicine was established and in 1881 a department of English language was established. In education, the university attached much importance to English study. English was one of the required courses and most courses were taught in English. Since the English levels of the graduates from the university were the best in China, they were welcomed by various enterprises.

In the 20^th century, the university made great efforts in promoting education quality and expanding education scale. Four relatively independent colleges were established. They were College of Arts, College of Science, College of Medicine and the Seminary. After 1906, its graduates could go to universities in the U.S. for further study. In the mid 1940s, the scale of the university was further expanded.