The river is formed from the confluences of several upper tributaries, such as Blue Creek and Chan Chich (Rio Bravo) which have their sources in Guatemala's Petén Basin region, and Booth's River which originates in the western Belizean district of Orange Walk.

The river continues its northeastern course with few other settlements along its length until reaching its outlet in Chetumal Bay.

The city of Chetumal, capital of the Mexican state of Quintana Roo and the region's main port, lies close to this outlet.

[citation needed] The river is mentioned in a stanza of Belize's national anthem, Land of the Free:

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