Little Brier Run begins in a shallow valley in Jordan Township, Lycoming County, just south of Pennsylvania Route 118.
After this, the stream turns south and slightly west for several tenths of a mile before exiting the valley and receiving an unnamed tributary from the right.
The stream then crosses Hickory Nut Hill Road and turns south-southeast, reaching its confluence with Little Fishing Creek after a short distance.
[1] Little Brier Run joins Little Fishing Creek 18.90 miles (30.42 km) upstream of its mouth.
[4] In 2011, Mountain Gathering, LLC requested a permit to construct and then maintain and operate a 24-inch (60-centimeter) gas pipeline in the vicinity of Little Brier Run.
[8] Between its headwaters and its mouth, it is on the Pennsylvania Fish and Boat Commission's list of wild trout streams.