The Lamprey River supports a significant fishery. Shad, alewife, and Atlantic salmon are found up to the impassable Wiswall Dam in Durham. The river is also part of the anadromous fish restoration program, a cooperative state-federal restoration program which began in 1969. Naturally-reproducing species sought by fisherman include small and largemouth bass, chain pickerel, sunfish, American eel, and brown bullhead. The NH Fish and Game Department regularly stocks the river with shad, rainbow, brown and brook trout.
Fishing continues into the winter, with ice-fishing popular along the length of the segment.
To allow access for fishermen, Salmon Unlimited has negotiated agreements with private landowners along key areas of the river.