For most of its length, it runs parallel to J. P. Rizal Avenue to the north from East Rembo near Fort Bonifacio to Barangay Singkamas by the border with Santa Ana, Manila.

[2][3][4] Subsequent development of the Bel-Air Village by Ayala Corporation in 1957 has led to the closure of a segment of Pasig Line west of EDSA.

In 2014, under the Roadmap for Transport Infrastructure Development for Metro Manila and Its Surrounding Areas (Region III & Region IV-A; also known as the Metro Manila Dream Plan), the JICA study proposes a dual 2-lane elevated expressway from the intersection of Roxas Boulevard and Gil Puyat Avenue to the intersection of C-5 and this road for about 9.3 kilometers (5.8 mi).

It cuts across the northern portion of the city, traversing barangays Singkamas, Tejeros, Santa Cruz, Olympia, Valenzuela, Bel-Air, and Poblacion.

Heading east towards the intersection with Makati Avenue, Kalayaan is dominated by the Century City and Picar Place developments on the northern side.

It runs underneath the Kalayaan Flyover, heading towards the entrance to Bonifacio Global City, entering Barangay Pitogo and, therefore, Taguig.