It is named after San Juan de Dios, a Portuguese-born soldier that turned health-care worker of Spain.

The present college of San Juan de Dios Educational Foundation, Inc. (SJDEFI) was founded on the ideals of nursing and health care, which were pioneered in the Philippines by the Order of Friars Minor in 1578.

In 2016, San Juan de Dios College opened its Senior High School (Grades 11 and 12) program with strands Accountancy, Business and Management (ABM), General Academic Strand (GAS), Humanities and Social Sciences (HUMSS), Science, Technology, Engineering and Mathematics (STEM) and Technological and Vocational Livelihood (TVL).

On the same year, the General Academic Strand (GAS) was discontinued permanently due to huge number of classrooms.

In May 2020, San Juan de Dios College temporarily discontinued their entrance examinations due to the COVID-19 pandemic.