UE College of Liberal Arts was organized in 1948 when UE was still the Philippine College of Commerce and Business Administration − with Dr. Jose Ma. Hernandez as its first Dean − and became fully operative in 1949 with a faculty contingent of 65 and an enrollment of 309 students. The College received official government recognition and produced its first Associate in Arts graduate in 1950. When the PCCBA attained University status and became UE, the College took on the additional function of serving the general education needs of the other units. By 1952, the College was producing graduates of a four-year course. The College was renamed College of Arts and Sciences (CAS) in the 1970s, when it started offering Bachelor of Science degree programs.

The Deans who succeeded Dr. Hernandez were Dr. Conrado P. Aquino, who eventually became UE President; Dr. Maximo Ramos; Dr. Socorro C. Espiritu; Dr. Herminia M. Barcelona, who was later appointed Vice President for Academic Affairs; Dr. Rosario Lamug, who also succeeded Dr. Barcelona as Vice President for Academic Affairs; Dr. Gonzalo Lavarias; and Dean Carmelita S. Flores.

When the Caloocan Campus became academically autonomous, the extension unit of the College became a separate College of Arts and Sciences. CAS Caloocan’s first Dean was Dr. Juanito C. Diaz, followed by Dr. Julieta B. Samonte. Later on, CAS Manila Dean Carmelita S. Flores acted as concurrent CAS Caloocan Dean until Dr. Corazon G. Esclabanan took over as CAS Caloocan Dean. In 1996, Dr. Teresita E. Erestain became CAS Caloocan Dean until her retirement in June 2003, when she was replaced by Dean Eleanor R. Javier.

Today, the College of Arts and Sciences is not just a service college. CAS Manila offers four-year degree programs with majors in Broadcast Communication, Journalism, English, International Studies, Political Science, Legal Management, Biology, Mathematics, Psychology, Library and Information Science, and Hotel and Restaurant Management. It was accredited to level II status by the Philippine Association of Colleges and Universities Commission on Accreditation (PACUCOA).

CAS Caloocan offers the Bachelor of Arts in Communication Arts program, Bachelor of Science in Tourism Management, Bachelor of Science in Hotel and Restaurant Management and Certificate in Security Management. CAS Caloocan also handles the Elementary and High School Department (EHSD), through which the Caloocan Campus offers Elementary and Secondary Education.