The highway runs through York County; major towns and cities along the length of SR 109 include Wells and Sanford.

It is cosigned with SR 9 for the southernmost 2.17 miles (3.49 km) of its length and interchanges with the Maine Turnpike (I-95) at exit 19.

The highway continues into the town of Shapleigh, where SR 11 splits off to the north near Mousam Lake just south of the Acton border.

North of Acton, SR 109 crosses the Salmon Falls River into Wakefield, New Hampshire and becomes NH 109.

Its three-digit number indicates that it was originally an intrastate route, abruptly ending at the New Hampshire state line until NH 109 was later designated.