The Seneca River flows 61.6 miles (99.1 km)[3] through the Finger Lakes region of Upstate New York in the United States.

The river passes under Interstate 90, flowing northeast past Weedsport, across the middle of Cayuga County into Cross Lake.

It turns sharply north then east, past Baldwinsville and Liverpool, along the northern edge of metro Syracuse where it receives the outflow of Onondaga Lake.

The channel between Three Rivers and Cayuga Lake was widened and straightened to accommodate barges, and other reaches were bypassed via the construction of parallel canals.

Seneca Falls is the location of the only significant natural drop on the river, which was utilized in the early days to power water mills.

[18] Below Onondaga Lake, the Seneca River is moderately polluted by industrial and domestic waste, including high levels of mercury, PCBs, dioxin and ammonia.

[19] Parts of the river are infested by non-native zebra mussels, which have depleted the level of dissolved oxygen, impacting fish populations.

The population density of mussels in one particular section of the river below Cross Lake is considered among the highest in North America.