It drains a hilly area, mostly forested and agricultural, east of the Finger Lakes at the northern edge of the Susquehanna River watershed.

Originally the Otselic Creek began at Hatch Lake in the Town of Eaton.

The Otselic River now rises in Torpy Pond in southwestern Madison County, northeast of Georgetown, and meanders southwest through rich river bottom farmland.

The Otselic Valley runs through Georgetown, Otselic, Pitcher, Cincinnatus, Willet, Lisle, and Whitney Point, where it is impounded to form Whitney Point Reservoir.

The Otselic River holds both native brook trout and stocked brown trout in the upper reaches and warmer water species such as smallmouth bass, walleyes and northern pike in the lower southern sections.