Santiago–Tuguegarao Road starts at Mabini Junction, a roundabout intersection with Maharlika Highway and R.C.

In Kalinga, it traverses the lowland municipalities of Tabuk, the province's capital, and Rizal, away from their poblacions.

It then enters the province of Cagayan and traverses the municipalities of Enrile and Solana, where it turns east at its intersection with Cagayan–Apayao Road.

It crosses the Cagayan River through the Buntun Bridge and enters the city of Tuguegarao.

This bypass road is designated as National Route 53 (N53) of the Philippine highway network.