Sta. Cruz National High School was opened on July 1, 1950 situated at Rizal Street, Sta. Cruz, Davao del Sur which is now Sta. Cruz National High School - Senior High School. It was named Sta. Cruz Junior High School and was changed to Sta. Cruz High School after the first batch graduated in 1954. There were only 22 pioneering students during the first year of operation and luckily 16 of them graduated and were awarded diplomas on March 1954 (9 males and 7 females). Most of their parents were fishermen, farmers, laborers, and few government employees.

On February 20, 1964, the municipal council of Sta. Cruz passed resolution # 140, converting swampy portion of the municipal plaza along the shoreline into new school site. In November of the same year, the school was transferred to its new site covering an estimated area of 5000 sq.m. Its main building was composed of 8 classrooms, a library, and an administration office. The school population had reached to 1,216 students in 1970 and accordingly an expansion of their site was made to a total land area of 20,000 square meters including the municipal plaza by virtue of Deed of Donation. In 1985, Congress passed Batas Pambansa Blg. 431 dated June 30, 1985 converting the status of the school to a national high school. Thus the school was renamed or changed to Sta.Cruz National High School.