[10] The Iskut River's watershed covers 9,544 km2 (3,685 sq mi),[6] and its mean annual discharge is 457 m3/s (16,100 cu ft/s).

[11][2] The Iskut watershed is highly glaciated and is characterized by landscapes shaped by geologically recent glaciers and the Laurentide Ice Sheet as well as volcanism.

[13][14] The name of the Iskut River possibly comes from a Nisga'a word meaning "stinking", otherwise of unknown origin.

Cascade Falls also marks the transition between the upper and middle Iskut River drainage basins.

[43] Originating in Mount Edziza Provincial Park,[44] the Little Iskut River is a major tributary with a watershed area of 453 km2 (175 sq mi), about 5% glacier-covered.

[50][51] Extremely hot water, heated by magma of the Northern Cordilleran Volcanic Province, weeps out of a rocky embankment and into the Iskut River.

[16][2][11] Near Bob Quinn Lake the Iskut is joined by one of its largest tributaries, the Ningunsaw River, flowing from the southeast.

[16] After the Ningunsaw confluence the Iskut River turns southwest, flowing through a braided channel and receiving the waters of Estshi Creek.

The largest is the Forrest Kerr Project, which diverts a portion of the Iskut River into a 3 km (1.9 mi) tunnel leading to an underground hydroelectric powerhouse.

There are ongoing studies to assess whether modifications to the river in the canyon and to the Forrest Kerr diversion weir could allow fish migration into the middle Iskut watershed.

The lower Iskut is part of a shared transitional zone between the interior plateau Tahltan and the coastal Tlingit people.

In protohistoric times the Tlingit ascended the Stikine River and its tributaries, including the lower Iskut, in large canoes during the summer to dry salmon and berries.

In the winter the Tahltan had exclusive use of the lower Iskut and Stikine for fishing, hunting, and trapping, as far downriver as the Stikine–Iskut confluence.

[87] The Tahltan traded caribou and moose hides, furs, sinew, babiche, obsidian, snowshoes, and other items to the Tlingit in exchange for fish oils, dentalia and haliotis shells, knives, axes, wooden boxes, woven baskets, Chilkat blankets, and other ceremonial items.

Most of the Iskut River's watershed was inhabited by the Tahltan Tuckclarwaydee (also called "Naskoten") band of the Chiyone (wolf) clan or moiety.

Tlingit Chief Shakes controlled trade up the Stikine and Iskut Rivers, which largely consisted of Western goods exchanged for furs.

[87] In 1838 Robert Campbell of the HBC made contact with the Tahltan from the interior, seeking to establish trading relations.

[87] In the late 1830s the HBC and RAC clashed over control of the coastal fur trade in the Stikine River area.

In 1839 an agreement was reached in which the HBC leased a section of the coast and gained access to the Stikine River trade.

The HBC acquired an RAC outpost at present Wrangell, Alaska, and named it Fort Stikine.

Diseases also spread from the coast into the interior, causing a drastic reduction in both Tlingit and Tahltan populations.

In the 1950s scientists began studying the area's significant wildlife ecosystems, eventually leading to the establishment of Spatsizi Plateau Wilderness Provincial Park in 1975.

[8] Many other fish species are present in the Iskut watershed, including cutthroat trout, three-spined stickleback, and kokanee salmon.

There are ongoing studies to assess whether modifications to the river in the canyon and the Forrest Kerr diversion weir could allow fish migration into the middle Iskut watershed.

Studies have shown that some sockeye and steelhead are keyed to the flow chemistry of the Forrest Kerr tailrace sufficiently to enter the power tunnel, which suggests that these fish originated above the canyon.

The upper Iskut region supports populations of wolverine, fisher, grizzly bear, Stone sheep, mountain goat, moose, woodland caribou, wolf, and hoary marmot, among many others.