Then-Rector Fr. Silvestre Sancho, O.P. created the Mathematics and Physics Department in 1938 to attend to the math and physics requirements of the College of Science. The degree B.S. Mathematics and Physics was introduced in 1952 and was eventually split into B.S. Mathematics and B.S. Physics in 1966. The B.S. Physics program died a natural death, however. In response to the changing needs of the time, two new courses were introduced: B.S. Mathematics major in Actuarial Science in 1978 and B.S. Mathematics major in Computer Science in 1984. The B.S. Mathematics major in Computer Science was later changed to B.S. Computer Science. The latter merged with the newly formed Department of Information and Computer Studies.

In November 2001, the College of Science entered into a Memorandum of Understanding with the School of Science and Engineering of Ateneo de Manila University for the latter to assist the former in the development and implementation of a curriculum in B.S Applied Physics. In 2002, the BS Applied Physics major in Instrumentation program was offered.

In the years that followed, the Department of Mathematics and Physics continuously upgraded its curricular offerings to meet the changing demands of the global society. In the year 2009, a shift from theoretical to applied mathematics was implemented with the realignment of B.S Mathematics major in Actuarial Science to B.S Applied Mathematics major in Actuarial Science.

The development of Physics and Mathematics instruction capabilities in the university was greatly attributed to Rev. Fr. Ciriaco Pedrosa, O.P., the first physicist in the Philippines and who was chair of the Department of Mathematics and Physics for more than a decade, starting in 1967 until the 1970s. It is also a university-wide service department for various mathematics and physics related general education courses.