The local terrain is quite hilly, as a result of the drainage of the Shoal Creek watershed, causing widespread belief that this is the name's source.

Alternatively, there is the belief that it was named for Hillsborough, North Carolina, the home of some of the early settlers, including Hiram Rountree and John Nussman.

Illinois Route 127 enters Hillsboro from the northwest with IL 16 but continues south as Vandalia Road; IL 127 leads north-northwest 12 miles (19 km) to Raymond and south 20 miles (32 km) to Greenville.

[4] The Middle Fork of Shoal Creek passes just west of the city limits, flowing south toward the Kaskaskia River.

Lake Hillsboro is a smaller reservoir on a tributary of the Middle Fork, northeast of the city center.

The Bremer Wildlife Sanctuary,[14] north of Hillsboro, is the southeastern terminus of the Arches Rail Trail.