The Senior High School is a product of Republic Act No. 10533 or the Enhanced Basic Education Act of 2013 in an attempt to reform the Philippine educational system and raise its capabilities that are compatible with world standards. 

The Senior High School found its home in the former Grade School buildings in the Fr. Eusebio Salvador, SJ Campus – Berchmans Hall, Matteo Ricci Hall, and Kostka Hall, upon the transfer of the Grade School to Fr. William Kreutz, SJ Campus in 2016. Mr. Rey Reyes, Assistant Principal for Administration and Finance of the AdZU Junior High School, was appointed as the first Principal.  

The unit offered four (4) strands at its beginnings: Accountancy, Business, and Management (ABM), Humanities and Social Sciences (HUMSS), Information and Communications Technology-2D Animation (ICT-2D Animation), and Science, Technology, Engineering, and Mathematics (STEM) with STEM as the largest strand by population. In its first year, the SHS was divided into four departments only – one per strand. It was only in the next school year (SY 2017-2018) that the departments were further divided into its current structure.