The river flows north for some 505 kilometres (314 mi)[4] to its mouth at the Babuyan Channel near the town of Aparri, Cagayan.

It flows westward and joins the Cagayan River at Ilagan, Isabela, 200 kilometres (120 mi) from the mouth.

The Siffu-Mallig system lies on the slope of the Central Cordillera ranges flowing almost parallel to the Magat River.

The Cagayan River and its tributaries are subject to extensive flooding during the monsoon season in Southeast Asia from May to October.

Experts are specifically monitoring the lower reaches from Tuguegarao to Aparri and the alluvial plain from Ilagan to Tumauini, Isabela.

It supports the lives of numerous endemic and endangered species, like the Luzon bleeding-heart pigeon (Gallicolumba luzonica), Philippine eagle (Pithecophaga jefferyi) and a rare riverine fish, locally called ludong (Cestreaus plicatilis).

The river drains a fertile valley that produces a variety of crops, including rice, corn, bananas, coconut, mangoes, citrus and tobacco.

With worsening weather patterns and regular severe storms, even traditional agricultural means are insufficient to feed families although they were bountiful in the past century, leading to the more aggressive use of destructive techniques.

From mouth to source: The Pan-Philippine Highway generally follows the course of the river from Echague until the Magapit Suspension Bridge where it continues west.