The river travels in sequence through Barranquitas, the municipal boundaries of Orocovis, Corozal and Naranjito, Ciales, Morovis, Barceloneta and Manatí in Puerto Rico.

In the 1898 Military Notes on Puerto Rico by the U.S. it is written that the "Manatí River is bounded on the east 'south by the Sierra Grande and on the west by the Siales ridge.

It rises in the Sierra Grande, and parallel with the preceding river, it flows through Siales and Manatí, to the north of which latter town it empties into the Atlantic.

"[2] In mid 2018, the United States Army Corps of Engineers announced it had earmarked $1.2 million to study flooding on the river.

View of Río Grande de Manatí from Paseo Lineal Juan Antonio Corretjer in Ciales.