[2] The source of the river is located in the Espino barrio of San Lorenzo, Puerto Rico on the eastern slopes of the Sierra de Cayey mountain range, close to Carite State Forest.

The river flows northeastwardly through the San Lorenzo batholith, a hilly region of intrusive igneous rock, where it meets with the tributaries of Emajagua and Cayaguas.

The river finally flows into San Juan's urban area and the Northern Plain of Puerto Rico where it discharges into the Atlantic Ocean.

[2] The river is of historical importance due to the number of settlements, cities and towns that were founded along it such as San Lorenzo, Caguas and Trujillo Alto.

[4] 18°26′18″N 65°52′42″W / 18.4382795°N 65.8782200°W / 18.4382795; -65.8782200[5]In mid 2018, the United States Army Corps of Engineers announced it would be undertaking a major flood control project of the river, with a budget of $250 million.