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The largest factor in finding fish on Pickwick Lake is water current. Produced by power generation at Wilson Dam, current stimulates forage which, in turn, stimulates predatory fish into feeding. Current breaks, slackwater areas adjacent to moving water, and any structure that interrupts current flow should be concentrated on and fished carefully. Fish position themselves in low flow areas facing into the deflected current.

Largemouth bass and smallmouth bass are the most sought after species by anglers. Pickwick Reservoir's greatest reputation is its superb smallmouth bass fishing. A 14-inch minimum size restriction limits harvest of smallmouth bass in Alabama controlled waters. One of the most popular smallmouth fishing areas is the "Shoals" section directly downstream of Wilson Dam to the end of Seven-Mile Island. Generation discharge from Wilson Dam creates a strong current in this area that smallmouth bass love. The middle to lower reaches of Pickwick provide excellent habitat for both largemouth bass and smallmouth bass. Smallmouth bass habitat in Pickwick Lake is so good that several line class records have been certified by the International Game Fish Association.

Crappie are another favorite fish species sought by anglers. The majority of the crappie angling in Alabama occurs during the spring on Bear Creek and Second Creek embayments. Most of the successful anglers drift jigs and minnows along the creek channels to find concentrations of crappie. Crappie must be longer than nine inches to be harvested from Pickwick Lake.

The tailwaters of Wilson Dam provide excellent opportunities to catch sauger during the winter months when they migrate upstream to spawn. Blue catfish and channel catfish are also found in high numbers during the summer. Bank access is available on the south side at Sheffield and Muscle Shoals. Florence (McFarland Park) and Waterloo provide fishing on the north side. Boat anglers can use Wilson Lock to fish Wilson Lake.

It is illegal to possess any Smallmouth Bass less than 14 inches in total length or any Crappie less than 9 inches in total length. There's a reciprocal license agreement with Mississippi and Tennessee for the Pickwick Lake area.

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