The first college branch of UP in Pampanga, the UP College Clark Air Base (UPCCAB), is established in June 1953 as an extension of the main campus in Diliman. It operated as a joint project of the University and of Clark Airbase to promote high level cultural relationship and exchanges between citizens of the Philippines and of the United States of America. Degree programs and courses offered at the Diliman campus may also be offered at the UPCCAB at the request of students. As per agreement between UP and Clark Air Base, UPCCAB accepts enrollment of US military and AFP personnel stationed in Clark. In 1979, UP Extension Program in San Fernando (UPEPSF) is established to absorb students from the province thus lessening the load of UP Diliman.
The eruption of Mount Pinatubo stopped the function of UPEPSF and UPCCAB on June 1991. The highly destructive volcanic eruption caused widespread damage and numerous deaths across Central Luzon. In October 1995, Pampanga was struck by Typhoon Sibyl (Mameng) which brought massive lahar flows and torrential rainfall. The old building of UPEPSF got submerged in lahar coming from the eruption of Pinatubo in 1991.
Eventually, UPEPSF transferred to Clark Special Economic Zone in 1996 and was renamed to UP Diliman Extension Program in Pampanga (UPDEPP). At the present, the permanent campus of UPDEPP is defined by the the Memorandum of Agreement signed by then Clark Development Corporation President Liberato P. Lapus and U. P. President Emerlinda R. Roman on April 2007. UPDEPP is located at the Clark Special Economic Zone which is less than 20 kilometers north of Manila. It is a 3.28-hectare lot along Claro M. Recto Highway and Ramon Magsaysay Extension, Clark Freeport Zone, Pampanga. The UP Clark campus embodies the visions of its host province, Pampanga, and the rest of Central Luzon.