Their native range includes a broad area west of the Appalachian Mountains encompassing large rivers of the Mississippi, Missouri, and Ohio basins. The range extends as far north as North Dakota, as far west as Arizona, and south to the Gulf of Mexico including northeastern Mexico.
Flathead catfish are most closely related to the Satan genus of fish. They grow to a length of 155 cm (61 in) and may weigh up to 56 kg (123 lbs). Their maximum recorded lifespan is 20 years. Males are mature from 16 cm and 4 years of age while females mature from 18 cm and 5 years of age, but may mature as late as 10 years. The world angling record flathead catfish was caught May 14, 1998 from Elk City Reservoir, Kansas and weighed 123 lb 9 oz (56.05 kg).
Inhabiting deep pools, lakes,and large slow-moving rivers, flathead catfish are popular among anglers; their flesh is widely regarded as the tastiest of the catfishes. Their size also make the flatheads effective subjects of public aquaria. Like most catfish, flatheads are benthic feeders and prefer live prey. They are voracious carnivores and feed primarily on other fish, insects, annelid worms and crustaceans.
Sport fishing for flathead catfish using either rod and reel or bare hands (noodling) can be an exciting pastime. Anglers target this species in a variety of waterways including small rivers (barely large enough for a canoe), large rivers (such as the Missouri and Mississippi Rivers), and reservoirs. A common element of flathead catfish location is submerged wood cover such as logs and rootwads which often collect at bends in rivers. A good flathead spot usually also includes relatively deep water compared to the rest of a particular section of river, a moderate amount of current, and access to plentiful baitfish such as river herring, shad, carp, drum, panfish, or suckers. Anglers targeting large flathead catfish usually use stout tackle such as medium-heavy or heavy action rods from 6–10 feet (1.8–3.0 meters) in length with large line-capacity reels and line ranging from 20–80 pound (90–360 N, 9–36 kgf) test breaking strength. Generally large live baits are preferred such as river herring, shad, sunfish (such as bluegill), suckers, carp, goldfish, drum, and bullheads ranging from 5–12 inches (12–30 cm) in length. Sometimes nearly as much time and effort is spent catching baitfish ahead of time as is spent fishing for flatheads. While not as numerous as other catfish species, catching a large flathead catfish (over 20 pounds) usually makes the effort worthwhile to an avid catfisher. Flathead catfishing often takes place at night either from a boat or from shore once a catfisher has identified a likely looking flathead spot.
Spawning occurs in late June and early July, the nests made in areas with submerged logs and other debris. The males, who also build the nests, fiercely and tirelessly defend and fan the clutch. The size of the clutch varies proportionately to the size of the female; an average of 2,640 eggs per kilogram of fish are laid.
The fry frequent shallow areas with rocky and sandy substrates where they feed on insects and worms such as annelids and polychaetes. Young flatheads are also cannibalistic, a fact which has largely precluded their presence in aquaculture.