The drainage basin of Buffalo Creek upstream of State Route 3005 is designated as a High-Quality Coldwater Fishery and a Migratory Fishery. Between State Route 3005 and Rapid Run, the drainage basin is designated as a Coldwater Fishery and a Migratory Fishery. Downstream of this point, the watershed is designated as a Trout-Stocked Fishery and a Migratory Fishery. Wild trout naturally reproduce in the creek from the headwaters downstream 8th Street bridge in Mifflinburg, a distance of . Half of the Pennsylvania Fish and Boat Commission approved trout waters in Union County are in the watershed of Buffalo Creek.