Most of the highway existed back to the
American colonial era as part of
Highway 21 that linked the city of
Manila to the provinces of
Rizal and Laguna by circumscribing
Laguna de Bay. The Calamba–Calauan segment of the highway was part of the Manila South Road system prior to the completion of the present-day section of the
Pan-Philippine Highway from
Santo Tomas, Batangas to
San Pablo, Laguna during that era. The entire road formed part of what was known as the
Calamba–Santa Cruz–Rizal Boundary Road. Roads bypassing the
poblacions of Santa Cruz, Calauan, and Bay were later built to form the present-day highway alignment. As of 2026, the
Department of Public Works and Highways (DPWH) revised the western terminus of the Calamba–Pagsanjan Road from its junction with J.P. Rizal Street and Real Road (officially known as Rizal Shrine Road) to its intersection with Manila South Road, both at the Calamba Crossing, incorporating a segment of the latter into its alignment. == Intersections ==