The highway reached its maximum length in 1967, and remained unchanged until 1997, when a section through Timmins was transferred to the responsibility of that city.

Initially proceeding north, the route quickly turns eastward in Wawa and enters the barren expanses of the boreal forest, travelling through uninhabited wilderness for much of its journey across the Canadian Shield.

Approximately 19.0 kilometres (11.8 mi) east of Wawa, the route encounters Highway 547, which travels north to Hawk Junction.

Just east of The Shoals Provincial Park, the highway crosses the Laurentian Divide, the boundary between the Great Lakes and Arctic Ocean watersheds; a sign and a small picnic area mark the transition.

Prior to entering the town, Highway 101 branches eastward, passing north of Chapleau Airport and resuming its course through the wilderness.

[1] East of Gervais Street North, Highway 101 travels northeast to Hoyle, passing beside several large open pit mines on the outskirts of Timmins.

The route passes through the only agricultural area along its journey, travelling straight for the remainder of the distance to Highway 11 west of Matheson.

[2][9] During World War II, plans arose to connect Timmins with the Quebec border, and the route via Matheson was chosen as the most direct path.

[19] In addition, a new 40.2 km (25.0 mi) road west of Chapleau was assumed in December, terminating at the Grazing River near the present entrance to The Shoals Provincial Park.

[3] A 21.3-kilometre (13.2 mi) segment of Highway 101 was transferred to the City of Timmins on April 1, 1997 as part of a province-wide downloading program.

The discontinuous section begins 200 metres (660 ft) east of Kamiskotia Road near Mountjoy and continues to Gervais Street North in Porcupine, encompassing a majority of the portion within urban Timmins.