St. Jude College was established in honor of St. Jude Thaddeus, the Apostle and Patron Saint of the Hopeful and the embodiment of the true Christian spirit. Through its allied health services, it started as the St. Jude Maternity Clinic in 1950. Faced with the growing health needs of the community and the breakthroughs and advances in allied medical sciences, the founders, Dr. Ramon D. Atienza, Jr. and his wife, Dr. Felicidad Calip-Atienza, expanded the Maternity Clinic from a two-storey building to a five-storey building with a 120-bed capacity. Later, they built an eight-storey building to house the School of Nursing. The two edifices were inaugurated on the feast day of St. Jude Thaddeus on October 28, 1968. As a result, the Maternity Clinic was elevated to the status of a College for consistently producing outstanding students and exemplary topnotchers in the licensure or board examinations since 1971.

Through the years, with the sheer dedication and passion of the founders, an additional eight-storey building, was erected to comprise the Main Building in 1977. By then, baccalaureate courses such as BS in Secretarial Administration, BS in Commerce, BS in Business Administration, BS in Nutrition and Dietetics, BS in Nursing and Bachelor of Arts Major in English, Filipino, History and Psychology were already being offered. Further, it had also offered its first masteral course, Masteral in Hospital Administration and two-year associate courses in Junior Secretarial, Dietitian Aide and Health Aide.

In 1985, government permits were granted to the college to open the following courses: Associate in Hotel and Restaurant and Management, Associate in Radiologic Technology and Master of Arts in Teaching Nursing Education. Courses such as Midwifery, BS in Civil Engineering, BS in Industrial Engineering, Associate in Tourism and BS in Hotel and Restaurant Management were likewise granted their respective government permits in the late 80s. Due to the rapid expansion of academic courses, another eight-storey building was constructed between the existing Main College Building and the Nursing Building in 1992. This is presently the Physical Therapy Building.

With a vision for a progressive, proactive and dynamic education and the mission of upholding academic and clinical excellence, courses such as BS in Physical Therapy and BS in Computer Science were offered in 1995. A year later, the eight storey Atienza-Calip Building was constructed.