Its southern foot just crosses the Mason–Dixon line near Flintstone, Maryland, running north 130 km (80 mi) to the Seven Mountains of central Pennsylvania, near Tusseyville, making it one of the longest named ridges in this section of the Ridge-and-valley Appalachians.

Tussey Mountain lies in, and the ridge line forms parts of the borders of, Centre, Blair, Bedford and Huntingdon counties.

At Everett the Pennsylvania Turnpike, U.S. Route 30, and the abandoned Huntingdon and Broad Top Mountain Railroad follow the Raystown Branch Juniata River through a deep water gap known as The Narrows.

Pennsylvania's longest footpath, Mid State Trail, is atop or closely parallels Tussey Mountain for nearly its entire length.

[citation needed] Pennsylvania State Game Lands Number 118 is located along Tussey Mountain in Blair and Huntingdon Counties.

The Tuscarora Quartzite is more resistant to erosion than Bald Eagle Sandstone, and both are more durable than the Juniata Shale sandwiched in-between.