It begins at the hamlet of Lyons in nearby Wayne County and meanders for approximately 27 miles (43 kilometers) from west to east before emptying into the Seneca River in the town of Tyre at Montezuma National Wildlife Refuge.

The Clyde River officially begins in the Wayne County hamlet of Lyons at the confluence of the Canandaigua Outlet and Erie Canal, just east of Lock #27.

Nearby Ganargua Creek is also part of the source feeding the Clyde River which empties into the Erie Canal 1/3 mile west of the lock.

First are the Canandaigua Outlet and Ganargua Creek which are part of the confluence with the Erie Canal to form the Clyde River in Lyons.

Before the Erie Canal was constructed in 1817, the Canandaigua Outlet and Ganargua Creek met in the village of Lyons to form the Clyde River.