Panther Run begins in a valley in Haines Township, Centre County.
It flows east-northeast for a few tenths of a mile before entering Hartley Township, Union County.
Here, the stream continues to flow east-northeast for a few miles.
It then begins flowing southeast past Buck Ridge.
The stream then enters The Hook, where it receives Slide Hollow, its only named tributary, from the left.
It then turns southwest for a few tenths of a mile before reaching its confluence with North Branch Buffalo Creek across from Dogback Mountain.

Panther Run joins North Branch Buffalo Creek 9.42 miles (15.16 km) upstream of its mouth.
Panther Run begins in a valley in Haines Township, Centre County. It flows east-northeast for a few tenths of a mile before entering Hartley Township, Union County. Here, the stream continues to flow east-northeast for a few miles. It then begins flowing southeast past Buck Ridge. The stream then enters The Hook, where it receives Slide Hollow, its only named tributary, from the left. It then turns southwest for a few tenths of a mile before reaching its confluence with North Branch Buffalo Creek across from Dogback Mountain.
Panther Run joins North Branch Buffalo Creek 9.42 miles (15.16 km) upstream of its mouth.
Panther Run