The school started with one office and four rooms. The first batch of 19 graduates in 1978 were those absorbed from the General Academic Curriculum.

The University Science High School was established by virtue of the approval of BOR Resolution No. 1622 by the CLSU Board of Regents on June 14, 1976, during the incumbency of the University President Amado C. Campos. Dean Conchita M. Cruz of the College of Arts and Sciences was designated coordinator while Dr. Belgrano T. Cajigal, Principal of the University Agricultural School, was assigned concurrently as the USHS Principal.

In 1978, BOR Resolution No. 1780 calling for the changing of the USHS to Agricultural Science High School was approved. The curriculum was revised and enriched in 1979 to strengthen its agricultural component to meed the needs of students who sought admission in agricultural institution of higher learning without prejudice to its original role of preparing the youth for intensive training in Science and Technology. The school opened its doors to first year applicants who qualified in the xcreening and passed the entrance examination. The slot was limited to 80. However, additional 10 slots for children of faculty and staff who ranked top 10 after teh 80th slot were alloted, hence, a total of 90 first year students.

The school expanded to two section per year level in SY 1980-81. Faculty members from different colleges/units were tapped to fill in the need for teachers. The school became an independent unit and was represented in the University Executive Committee, now the University Administrative Council of Deans.

In 1983, the school was given back its original name, University Science High School, to underscore the school's emphasis on Science, Technology and Communication.

With the birth of the NCC evaluation of the faculty during the SY 1986-1987, the school was attached to the College of Education as its laboratory school. However, it remained headed by a principal, who represented the Unit in the Administrative Council and the Council of Deans and Directors of the University. In 1999, the Department of Education, Culture and Sports declared the USHS as one top performing high schools in the Philippines.

Several curriculum revisions have been made to keep abreast with the needs of the changing times and the students.

Now, on its 30th year of existence, the USHS as premiere high school in the country has always been and will always be contributing to the image building of the University. The school has produced quality and honor graduates who have carved niches in their fields of specialization in private and government institutions here and abroad. The USHS has vowed to continue its mission of providing Excellence and relevance in secondary education in this part of the country.