North Branch Mehoopany Creek has a deep, narrow valley, with "rough and hilly" topography.

North Branch Mehoopany Creek begins in Wilmot Township, Bradford County.

The highest average discharge for an individual month was 294.7 cubic feet per second (8.34 m3/s), which occurred in April 1958.

[4] In the early 1900s, the average annual rate of precipitation in the watershed of North Branch Mehoopany Creek is 35 to 40 inches (89 to 102 cm).

[5] The elevation near the mouth of North Branch Mehoopany Creek is 755 feet (230 m) above sea level.

The creek has a channel that is sinuous and flows through rock formations consisting of sandstone and shale.

In the 2000s, accelerated erosion of streambanks and lateral shifting were identified at five locations on North Branch Mehoopany Creek.

This was caused by man-made alterations after Tropical Storm Agnes in 1972 and other flooding events, as well as dredging in the creek.

[9] North Branch Mehoopany Creek was entered into the Geographic Names Information System on August 2, 1979.

[6] The latter variant name appears in a 1983 county highway map created by the Pennsylvania Department of Transportation.

[14] In the early 1900s, the main industry in the watershed of North Branch Mehoopany Creek was agriculture.

[5] A two-span prestressed box beam or girders bridge carrying State Route 3001 over North Branch Mehoopany Creek was built in Forkston Township, Wyoming County in 1987 and is 89.9 feet (27.4 m) long.

[15] A steel stinger/multi-beam or girder bridge carrying T-410 over the creek was built in Colley Township, Sullivan County in 1925 and is 33.1 feet (10.1 m) long.

[8] Wild trout naturally reproduce in North Branch Mehoopany Creek from its upper reaches downstream to its mouth.

[21] In the 2000s, a total of 31 species of fish were observed in the creek, including darters, daces, suckers, and bluegills.

[9] North Branch Mehoopany Creek is too small to support viable hellbender populations, even at its mouth.