Traversing the provinces of Benguet, Pangasinan, and Tarlac, it is one of the largest river systems in the country, with a drainage area of 5,952 square kilometres (2,298 sq mi).

[6] Roughly two million people live in the Agno River Valley, making it one of Philippines' larger population clusters.

The swamp has an area of about 25 square kilometres (9.7 sq mi) and temporarily retains flood waters from Tarlac River.

After passing through mountains at an average elevation of some 2,000 feet (610 m) ASL, the Agno River forms a vast alluvial fan and delta called the Pangasinan Plain, a historically vital economic hub on Luzon Island.

The river's headwaters and upstream basin in the Cordillera Central range are designated conservation areas that lie within the Mount Data National Park, the Upper Agno River Basin Resource Reserve and the Lower Agno Watershed Forest Reserve.

Spanish explorers who documented the catchment area of the river in the 16th century say the mouth of the Agno was an extensive marshland with rich alluvial soil.

It was thickly covered with mangrove and nipa palm trees which served as habitat to many marshland wildlife species.

The catastrophic floods of July–August 1972, May 1976, and September 2009 inundated the entire Pangasinan Plain, including the floodplains of the Tarlac River.

The Agno traverses several towns in Benguet province where some 35,000 indigenous Ibaloi, Kankanaey and Kalanguya people live.