Rizal State College Antipolo was established and initially operated at the five loaned rooms in Antipolo National High School. After which, it occupied the Rizal Technological University located at Marigman St., Brgy. San Roque, Antipolo City, the current seat of the campus. Initially, Antipolo Campus was led by RSC campus director, Mr. Amor David Mercado in 2000-2002.

In October 2001, RSC Antipolo Campus was enacted as one of the campuses of the University of Rizal System under Republic Act 9157. In 2002-2003, the university was led by the transition president, Atty. Lilia S. Garcia while the campus was supervised by Ms. Aileen Gutierrez as campus coordinator on March-May 2003. After which, Dr. Olivia F. De Leon served as the first university president. URS Antipolo Campus smoothly operated in the city under the baton of the campus directors, Dr. Allen U. Bautista from 2003 to 2005 and Dr. Rowena Dr. Laroza from 2005 to 2007.

The University's organizational structure was modified in which the campuses are divided into three clusters. URS Antipolo Campus became part of Cluster III under the leadership of Dr. Gloria P. Sarabia from 2007 to 2011 and Dr. Juan O. Abarro from 2012 to 2013. Alongside the restructuring of the organization was the leader of the campus deans. The first campus dean was Dr. Digna C. Ramos from 2007 to 2009, followed by Prof. Mylen E. Balagot from 2009 to 2011, Prof. Jonah O. Bautista as OIC dean from 2011-2012, and Engr. Armando D. Vale from 2012 to 2013.

When Dr. Marita R. Canapi took lead in the University, the clustering of the campus and managing of the campus deans were retained on its original organizational structure, in which, from 2013 to 2014, Dr. Marinette Ramos became the campus director. When Dr. Ramos was appointed to another campus, Dr. Danilo M. Pascual was appointed as the new campus director up to the present.