Built as part of the 2.7-kilometer (1.7 mi) NLEX Segment 8.1 of the Harbor Link project extending the expressway to Mindanao Avenue,[2] which has since been incorporated into the C-5 system, it is the Philippines' largest cloverleaf interchange in terms of land area.

[5][6] Construction of NLEX Segment 8.1, including the present-day Harbor Link Interchange on the same proposed site, broke ground on April 2, 2009,[7] with actual construction work beginning 19 days later.

[8] The entire segment was opened to traffic on June 5, 2010, with President Gloria Macapagal Arroyo and Manuel V. Pangilinan, chairman of the Manila North Tollways Corporation, the concessionaire of the North Luzon Expressway, leading the inauguration along with Public Works and Highways Secretary Victor Domingo and high-ranking officials from Valenzuela.

[9] With some 30,000 vehicles estimated to use the new road daily during its first year of operation,[8] since its opening, it has helped to relieve traffic on the older Balintawak Interchange connecting Epifanio de los Santos Avenue (EDSA) to NLEX,[10] which is three times smaller.

[15][16] On June 21, 2021, as part of a greening initiative led by NLEX Corporation, the Department of Environment and Natural Resources, and House Deputy Speaker Eric Martinez (Valenzuela–2nd), 3181 saplings were planted at the interchange.