The College of Arts and Sciences was created by virtue of Section 7 of Republic act No. 4067 entitled “An Act Converting the Central Luzon Agricultural College (CLAC) into Central Luzon State University (CLSU)”, signed by the President Diosdado Macapagal on June 18, 1964. This provision empowered the Board of Regents to approve the establishment of, among others, The College of Arts and Sciences and its four departments: Behavioural Sciences, Biological Sciences, Humanities and Languages, and Physical Sciences. Since then, the college has expanded into a comprehensive college that offered various degree programs both in the sciences and the arts. To date, the college has nine departments namely: Biological Sciences, Chemistry, English and Humanities, Filipino, Mathematics and Physics, Statistics, Social Sciences, Psychology and Development Communication. It started offering B.S. Biology in 1981 and B.S. Chemistry in 1982. To face the challenges of time, the college offered additional curricula. These are AB Social Sciences in 1993, AB Development Communication in 1999, BS Statistics in 2000, AB Psychology in 2005, AB Language and Literature in 2010 and BS Environmental Science in 2012. The offering of the BS Environmental Science is in cooperation with the College of Agriculture and the College of Engineering. Besides offering the undergraduate degree programs and being the hub of the breeder sciences, the College of Arts and Sciences is the service college of the Central Luzon State University.

The Commission on Higher Education (CHED) designated the Departments of Biology and Chemistry as Centers of Development in Biology and Chemistry, respectively.