The trunkline runs between Interstate 75 (I-75) just north of Indian River and Cheboygan, where it meets US Highway 23 (US 23) near Lake Huron.

M-27 runs along the western shore of Mullett Lake and forms the main street of Topinabee.

The original M-27 was located in The Thumb, running from the Mount Clemens area east and north through New Baltimore to Port Huron.

There it ran through Carsonville and Minden City to Harbor Beach and along Lake Huron to Port Austin.

Where US 27 ran northwest through Topinabee to Cheboygan and then concurrently along US 23 to Mackinaw City, I-75 was built due north of Indian River before turning northwest parallel and several miles inland from Lake Huron, bypassing Cheboygan completely.