The Usumacinta River (Spanish pronunciation: [usumaˈsinta]; named after the howler monkey) is a river in southeastern Mexico and northwestern Guatemala. It is formed by the junction of the Pasión River, which arises in the Sierra de Santa Cruz (in Guatemala) and the Salinas River, also known as the Rio Chixoy, or the Rio Negro, which descends from the Sierra Madre de Guatemala. It defines part of the border between Guatemala and the Mexican state of Chiapas, then continues its northwesterly course, meandering through the Mexican state of Tabasco to the Gulf of Mexico.

The Usumacinta River enters Mexican territory in the state of Tabasco and across the Cañón del Usumacinta (Usumacinta Canyon) ecological reserve, forming impressive canyons along its route. Passing the canyon called "Boca del Cerro", Tenosique, the Usumacinta goes into the plain of Tabasco.

Two distributaries, the Palizada River and San Pedro y San Pablo River, branch from the main stem of the Usumacinta and empty north and east into the Laguna de Términos. In Tabasco the Grijalva River flows into the Usumacinta River. This confluence is at Tres Brazos, Centla, and the two rivers form a large wetland region known as the Pantanos de Centla. The pantanos (wetlands) are designated a biosphere reserve; it contains 302,702 hectares (747,990 acres), which makes it the largest protected wetland region in North and Central America and one of the top 15 wetlands (by size) in the world.

The total length of the river, including the Salinas, Chixoy, Negro rivers in Guatemala is approximately 1,000 kilometres (620 mi). It is the only visible natural boundary separating the Yucatán Peninsula from the rest of Mexico.

The river and its tributaries were important trade routes for the ancient Maya civilization. Yaxchilan and Piedras Negras, two of the most powerful cities of the Maya Classic Period, lie along its banks.

Before roads, such as the Border Highway constructed by the Mexican Government in the early 1990s, penetrated the jungle, the river was the only means of travel in this region. Huge trunks of hardwood trees were floated downriver to the state of Tabasco.

In the 1980s, many Guatemalan refugees fled across the river to relative safety in Mexico. Other groups of refugees and Guatemalan guerrillas formed the so-called CPR communities in the jungle on the Guatemalan shores, hiding from the government until the peace accords of the nineties.

Frans and Trudi Blom first brought the idea of conservation to the watershed in the 1950s by proposing that a section of the Selva Lacandona be reserved for the Lacandon Maya. Their idea was as much the preservation of culture as of habitat, and this principle – that indigenous integrity and habitat are inextricably linked in the watershed – should help guide any future conservation planning. Conservationists working in the region, such as Nacho March, Ron Nigh, Fernando Ochoa, Roan Balas McNab and others, have all acknowledged and upheld the principle in their work.