In its southern half, the MST mostly follows rocky ridgetops in the ridge and valley province and reaches dozens of expansive vistas.

[2] The northern segment of the trail traverses slightly less rugged but still challenging landscapes on top of the Allegheny Plateau.

The MST then climbs up the next segment of Tussey Mountain and passes through multiple tracts of State Game Lands 73.

Above Williamsburg, the MST descends, follows rural roads and city streets through the town,[7] then joins the Lower Trail (a rail-trail) and walks easily for about 18 kilometers, alongside the Frankstown Branch of the Juniata River.

[7] North of US Route 22, the MST climbs up the next segment of Tussey Mountain and enters Rothrock State Forest.

[9] The trail then walks through Penn-Roosevelt State Park, and later uses a culvert to pass under the US Route 322 expressway near Potters Mills.

Winter State Park, the MST continues to climb up and down several different ridgelines and uses a rural road overpass to cross Interstate 80 to the east of its interchange with PA Route 880.

North of that park, the MST follows a segment of the Native American Great Island Path, reenters Bald Eagle State Forest, and descends to the valley of the West Branch Susquehanna River.

After continuing through some low valley areas with a few farms, the MST next reenters Tiadaghton State Forest and rises to the top of the Allegheny Plateau.

The trail skirts the west side of Hammond Lake, crosses PA Route 287 again, then continues north through lightly developed rural areas.

The MST then leaves the lake, continues to the north, and reaches the New York border after 526 kilometers (327 miles) in Pennsylvania.