The river's watershed – the Klamath Basin – encompasses more than 15,000 square miles (39,000 km2), and is known for its biodiverse forests, large areas of designated wilderness, and freshwater marshes that provide key migratory bird habitat.

Violent conflict and displacement of tribes occurred during the California Gold Rush as prospectors pushed into the lower Klamath basin, leading to a bitter fight over establishing reservation lands.

In the early 20th century, the federal government drained the upper basin's once extensive lakes and wetlands for agriculture, while private utilities constructed hydroelectric dams along the river.

The river empties into the Pacific Ocean at a tidal estuary near Requa,[20] in an area shared by the Yurok Reservation and Redwood National and State Parks,[21] about 16 miles (26 km) south of Crescent City.

Situated between the Cascades and the Oregon high desert and northwest of the Modoc Plateau, it features a semi-arid climate and is characterized by large, flat alluvial valleys separated by long mountain ridges.

[62][63] When the Klamath encountered this layer, it began cutting its canyon along the mica instead of continuing southwest to the Pacific, resulting in the sharp northward bend where the Trinity River joins.

Traditional ecological knowledge describes the type of natural science information that indigenous people have gathered about the places they live in over the course of hundreds, if not thousands, of years.

Although the term "world renewal" was coined by anthropologist Kroeber and Gifford, the Karuk tribe has adopted the phrase to refer to their annual ceremony that they view as essential to maintaining the reciprocal and stewarding relationship they have with the environment.

[80] The Hupa Valley tribe hold similar ceremonial and religious beliefs regarding the river as the Yurok and Karuk people, including practices of jump dances and cultural/subsistence reliance on the Klamath's salmon runs.

[87] In 1905, the United States Forest Service, an agency of the Department of Agriculture headed by Gifford Pinchot – a prominent conservationist and staunch opponent of burning – began to manage what was traditionally Klamath lands.

[97] Fur trappers eventually moved southwest into the Sacramento Valley and extended the Siskiyou Trail, an early path between the Oregon Territory and San Francisco Bay.

Beaver dams had previously been an important factor in stream habitat in the Klamath River watershed, helping to moderate the power of floods and creating extensive wetlands.

Though carrying a large volume of water, it has nearly everywhere a considerable grade and velocity of current with no great depth ... ... At the present time there are about twenty-five claims being worked on the Klamath and Salmon Rivers, employing three hundred men.

[107] Additionally more indigenous land was lost in the 1970s after the completion of the construction of a section of highway 96 which ran through traditional Karuk territory and paved over cemeteries, villages, spiritual sites and allotments.

Prior to the cut, south winds sometimes pushed water out of the lake's shallow outlet, causing the Link River to run dry – a phenomenon reflected in the stream's native Klamath name, Yulalona, "back and forth".

In 1957, California and Oregon signed the Klamath River Compact, which gave preference to the "higher uses" of domestic and irrigation water supply, over the "lower uses" of recreation, fish and wildlife, industry and power generation.

[120] Even though the Klamath were forced to surrender treaty lands in the mid-20th century, the tribes' water rights were upheld in a 1983 court decision (United States vs. Adair), and Oregon formally quantified their share in 2012.

In a 1951 report titled the United Western Investigation, the Bureau of Reclamation proposed building the enormous Ah Pah Dam that would have diverted almost the entire flow of the Klamath and Trinity Rivers to Southern California.

However, the dam was opposed by one of its chief beneficiaries – the Metropolitan Water District of Southern California, representing Los Angeles and numerous other cities – who believed that the Klamath project would be used to pressure it into giving up its share of the Colorado River.

[24][133] Prior to Iron Gate's construction, discharge from the Copco dams fluctuated greatly due to peaking power operation, creating hazardous conditions for fishermen and other people using the river.

[27] Despite the great reduction in wetlands over the 20th century, the Upper Klamath Basin still hosts large concentrations of migrating waterfowl,[31] with as much as 80 percent of birds along the Pacific Flyway passing through.

[137] These areas also provide habitat for large mammals such as deer, elk, antelope, bear and cougar; fur-bearers including muskrat, beaver and mink; and upland game birds such as doves, pheasant, grouse and quail.

[33]: 1.9  Reservoirs and lakes in the Upper Basin host many species of nonnative warm-water game fish, including yellow perch, brown bullhead, and pumpkinseed.

In 1972, following the controversial arrest of a Yurok subsistence fisherman, the Supreme Court ruled in Mattz v. Arnptt that the state did not have jurisdiction over tribal fisheries, as Indian reservations were created by federal executive order.

[145] In 1977 the U.S. Bureau of Indian Affairs took over management of the tribal fishery and reopened the lower river to fishing, but it was closed again the next year after conservation groups objected.

In 1991, Congress passed the Central Valley Project Improvement Act, directing the Bureau of Reclamation to increase minimum Trinity River flows over a five-year period.

[33]: 2.5 [148] With restoration efforts, the fall Chinook run recovered to 150,000 per year by the 2010s, with the Klamath, Trinity, Salmon, Scott and Shasta rivers all hosting spawning populations.

[33]: 1.15  While most of the natural range of Klamath coho has never been blocked by dams, they have been impacted more severely by habitat degradation related to mining and logging, as they spend more time in freshwater than Chinook.

[156] During dry seasons, the lower Klamath River also experiences elevated phosphorus and nitrogen levels from irrigation run-off, while toxic algae blooms result in eutrophication.

[33]: 2.4 [164] In 2020, the states of California and Oregon, the Yurok and Karuk Tribes, PacifiCorp, and the newly created Klamath River Renewal Corporation (KRRC) signed a final Memorandum of Agreement to implement the project.