Formed by the confluence of its east and west forks near the hamlet of Blossvale, the creek flows southwest for 11 miles (18 km),[6] through the towns of Annsville and Vienna.

The creek drains approximately 528.9 square miles (1,370 km2) of the Tug Hill plateau country in Central New York.

It flows generally south, receiving Sucker Brook from the east and entering a narrow gorge, where it is impounded in the small City of Rome Reservoir.

The West Branch rises in marshes near Williamstown in eastern Oswego County and flows in a generally southeasterly direction.

Most of the water in Fish Creek originates as snowmelt from the Tug Hill, a region renowned for its extremely heavy winter snowfall.

The Indians then drove all the fish (including prodigious runs of Atlantic salmon) from upstream down to the barrier before a second brush dam was constructed to trap them, at which point they were easily collected with spears and nets.

[19] Part of the East Branch was considered for National Wild and Scenic Rivers System designation in 1978, but was not passed due to a lack of local support.