The Pampanga River is the second largest river on the island of Luzon in the Philippines (next to the Cagayan River) and the country's fifth longest river. It is in the Central Luzon region and traverses the provinces of Pampanga, Bulacan, and Nueva Ecija.

Its headwaters are at the Sierra Madre and runs a south and southwesterly course for about 261 kilometres (162 mi) until it drains into Manila Bay.

The river's basin covers an area of 10,434 square kilometres (4,029 sq mi), including the allied basin of Guagua River. The basin is drained through the Pampanga River and via the Labangan Channel into Manila Bay.

Its main tributaries are the Peñaranda and the Coronel-Santor rivers on the eastern side of the basin and the Chico River from the northwest side. The Angat River joins the Pampanga River at Calumpit, Bulacan via the Bagbag River. Mount Arayat stands in the middle of the basin.

Southeast of Mount Arayat and the Pampanga River is the Candaba Swamp, covering an area of some 250 square kilometres (97 sq mi) absorbing most of the flood flows from the western slopes of a portion of the Sierra Madre and the overflowing of the Pampanga River via the Cabiao Floodway. This area is submerged during the rainy season but is relatively dry during summer.

The basin experiences, on an average, at least one flooding in a year. The dry season generally occurs from December to May and wet the rest of the year. The wettest months are from July to September. The Pampanga River Basin could handle between 100 and 130 millimetres (3.9 and 5.1 in) of 24-hour rainfall.

Extensive flooding occurred at the Pampanga River Basin in July 1962, May 1966, May 1976, October 1993, August 2003, August 2004, late September–October 2009, and August 2012.

The flooding in September 2011 associated with Pedring (Typhoon Nesat) nearly swallowed all of Pampanga and southern parts of Bulacan.