[4] The creek begins in a marshy area at Apulia Station, near State Route 80, as the confluence of a few seasonal streams that drain the nearby Truxton, Jones and Fellows Hills.

[6] However, the lower reaches of the creek are moderately affected by high nutrient levels from agriculture and urban runoff.

As the ice retreated about 12,000 years ago during the Pleistocene, Glacial Lake Newbury was formed to the west, in the present-day Syracuse area.

The lake was initially dammed on its east end by the hills between the Butternut and Onondaga Creek valleys.

[8] After the ice fully melted, the water drained northward into the Great Lakes and the Saint Lawrence River, leaving the now dry "Syracuse channels" – a series of large breaks between the Butternut and Onondaga valleys[9] – and a 180 foot escarpment at Clark Reservation State Park, which was once a giant waterfall fed by glacier melt.

[13] The reservoir has 224 acres (91 ha) of water, a capacity of 4,000 acre⋅ft (4,900,000 m3), and is bordered by Jamesville Beach County Park, a popular local swimming area.

The New York State Department of Environmental Conservation maintains 8.1 miles (13.0 km) of the creek for public fishing.