It drains a dissected plateau area in upstate New York at the northern end of the Susquehanna watershed.

Named after the Oneida word for bull thistle,[5] in the 19th century the Chenango furnished a critical link in the canal system of the northeastern United States.

From Morrisville, it flows south past Eaton and is paralleled by the remnants of the old Chenango Canal from Randallsville, just south of Hamilton, to just north of Earlville where the old canal joined the river.

It flows past Brisben and Greene to Chenango Forks, where, about nine miles north of Binghamton, it receives from the right its major tributary, the Tioughnioga River.

[7] It ends where it joins the Susquehanna from the north in downtown Binghamton in Broome County.