The town is named after the native Onondaga tribe, part of the Iroquois Confederacy.

Onondaga was incorporated April 2, 1798, and is located southwest of the city of Syracuse, which it borders.

The villages and hamlets which make up the town are: Cedarvale, Howlett Hill, Navarino, Nedrow, Onondaga Hill, Sentinel Heights, South Onondaga, Southwood, Split Rock, and Taunton.

The Onondaga region was within what was designated the Central New York Military Tract, in which the new government allotted land grants to veterans as payment for their war service.

In the postwar years, the area was flooded with migrants from New England and eastern New York.

After the county seat was moved to Syracuse in 1830, the building in Onondaga Hill was used as a school until 1846.

The Gen. Orrin Hutchinson House - which is now the Inn of the Seasons restaurant - at 4311 W. Seneca Turnpike is the only Town of Onondaga site listed in the National Register of Historic Places.

U.S. Route 11 is a north–south highway in the eastern part of Onondaga, paralleling the interstate.

The villages and hamlets which make up the town are: Cedarvale, Howlett Hill, Navarino, Nedrow, Onondaga Hill, Sentinel Heights, South Onondaga, Southwood, Split Rock, and Taunton.