The river begins near the boundary between the towns of Huntington and Westhampton, Massachusetts, and flows southeast to White Reservoir and then Tighe Carmody Reservoir in Southampton.

The river continues southeast, then turns northeasterly and flows through the middle of Easthampton to its confluence with the Connecticut River at a westward curve called The Oxbow.

The river provides excellent views of nearby Mount Tom.

In 1847 large mills began with the Williston-Knight Button Company; a number of other factories sprang up nearby in the next few years.

A former railroad has been converted to the Manhan Rail Trail, which now provides a scenic pathway along the river.