The river is considered a prime habitat for Chinook salmon, Coho salmon, and rainbow trout.
Once the river was the third-largest producer of salmon on the West Coast, after the Columbia and Sacramento Rivers, but the salmon run has been reduced since the construction of six dams between 1908 and 1962.
Coho salmon in the Klamath River are listed as threatened under the Endangered Species Act.
In 1963, the upper Trinity River—the largest single tributary to the Klamath—was virtually removed from the Klamath drainage with the completion of the Lewiston and Trinity Dams, diverting 90 percent of the upper Trinity's flow to the Sacramento Valley.
From 1963 to 1991, only 150 cubic feet per second (4.2 m³/s) from the main stem above the dams was left to flow to the Klamath.
In 1991, a minimum annual Trinity flow of 340,000 acre feet (420,000,000 m³) was established, or about 470 cubic feet per second (13 m³/s).

From the 1920s to the 1960s, four hydroelectric dams were built by the California-Oregon Power Company (COPCO) and its successor PacifiCorp on the Klamath River main stem, blocking salmon migration and trapping sediment that formerly replenished downstream gravel bars used by spawning salmon.
The possible removal of the dams has been a controversial issue in the region in recent years.
Despite intense lobbying by local Native American tribes, conservationists, and fishermen, the 2004 renewal application by PacifiCorp for another 50-year federal operating license for the dams did not include any provisions for allowing salmon to return to more than 300 miles (483 km) of former habitat above the dams.
 In January 2007, however, the federal government ruled that PacifiCorp must equip four dams with fish ladders, a modification which would potentially cost more than $300 million.
PacifiCorp has offered $300 million to upgrade the JC Boyle fish ladder and proposed trucking fish around the Copco Number 1 and Iron Gate dams, after having had been denied a license to build a power generator in Utah.
PacifiCorp President Fehrman defended the company's activities in the area, pointing to other benefits.

A separate controversy surrounds the use of water in the Upper Klamath Basin for irrigated agriculture, which was temporarily halted in 2001 to protect endangered salmon and lake fish during a severe drought.
Vice President Dick Cheney personally intervened to ensure water to the agriculture industry rather than to environmental flow.
In 2002, the federal government, under Interior Secretary Gale Norton, provided full water deliveries to irrigators as the drought continued; despite the fact that Klamath area tribes have treaty rights that predate the settlement of the farmers.
Norton argued for a "free market" approach by allowing farmers to sell the water to the Native Americans downstream.
That year, the Klamath River system had the largest fish die-off ever recorded.
 The House Natural Resources Committee investigated Vice President Cheney for having released extra water to ranchers for possible political gain.

According to biologists from the State of California and the U.S. Fish and Wildlife Service, the atypical low flow in the river along with high fish return numbers and high water temperatures allowed for a gill rot disease to kill at least 33,000 salmon in September 2002, before they could reproduce.
 The die-off was downstream of the Trinity inflow, and the salmon of the Trinity were impacted to a greater degree than the Klamath as the Trinity run was at its peak.
The report does mention that the official fish die-off estimate of 34,056 is probably quite low and could be only half of the actual loss.
Klamath River flows as measured at the river gauge in Keno show a low flow of 800 cubic feet per second (22.7 m³/s) in September 1908 (before irrigation began).
During the 2002 fish kill, flows of 475 cubic feet per second (13.5 m³/s) were recorded.
During September of the 2001 irrigation shut-off, an average of 688 cubic feet per second (19.5 m³/s) was recorded.

In 2011, the U.S. Environmental Protection Agency (EPA) approve
The river is considered a prime habitat for Chinook salmon, Coho salmon, and rainbow trout. Once the river was the third-largest producer of salmon on the West Coast, after the Columbia and Sacramento Rivers, but the salmon run has been reduced since the construction of six dams between 1908 and 1962. Coho salmon in the Klamath River are listed as threatened under the Endangered Species Act. In 1963, the upper Trinity River—the largest single tributary to the Klamath—was virtually removed from the Klamath drainage with the completion of the Lewiston and Trinity Dams, diverting 90 percent of the upper Trinity's flow to the Sacramento Valley. From 1963 to 1991, only 150 cubic feet per second (4.2 m³/s) from the main stem above the dams was left to flow to the Klamath. In 1991, a minimum annual Trinity flow of 340,000 acre feet (420,000,000 m³) was established, or about 470 cubic feet per second (13 m³/s).
From the 1920s to the 1960s, four hydroelectric dams were built by the California-Oregon Power Company (COPCO) and its successor PacifiCorp on the Klamath River main stem, blocking salmon migration and trapping sediment that formerly replenished downstream gravel bars used by spawning salmon. The possible removal of the dams has been a controversial issue in the region in recent years. Despite intense lobbying by local Native American tribes, conservationists, and fishermen, the 2004 renewal application by PacifiCorp for another 50-year federal operating license for the dams did not include any provisions for allowing salmon to return to more than 300 miles (483 km) of former habitat above the dams.  In January 2007, however, the federal government ruled that PacifiCorp must equip four dams with fish ladders, a modification which would potentially cost more than $300 million. PacifiCorp has offered $300 million to upgrade the JC Boyle fish ladder and proposed trucking fish around the Copco Number 1 and Iron Gate dams, after having had been denied a license to build a power generator in Utah. PacifiCorp President Fehrman defended the company's activities in the area, pointing to other benefits.
A separate controversy surrounds the use of water in the Upper Klamath Basin for irrigated agriculture, which was temporarily halted in 2001 to protect endangered salmon and lake fish during a severe drought. Vice President Dick Cheney personally intervened to ensure water to the agriculture industry rather than to environmental flow. In 2002, the federal government, under Interior Secretary Gale Norton, provided full water deliveries to irrigators as the drought continued; despite the fact that Klamath area tribes have treaty rights that predate the settlement of the farmers. Norton argued for a "free market" approach by allowing farmers to sell the water to the Native Americans downstream. That year, the Klamath River system had the largest fish die-off ever recorded.  The House Natural Resources Committee investigated Vice President Cheney for having released extra water to ranchers for possible political gain.
According to biologists from the State of California and the U.S. Fish and Wildlife Service, the atypical low flow in the river along with high fish return numbers and high water temperatures allowed for a gill rot disease to kill at least 33,000 salmon in September 2002, before they could reproduce.  The die-off was downstream of the Trinity inflow, and the salmon of the Trinity were impacted to a greater degree than the Klamath as the Trinity run was at its peak. The report does mention that the official fish die-off estimate of 34,056 is probably quite low and could be only half of the actual loss. Klamath River flows as measured at the river gauge in Keno show a low flow of 800 cubic feet per second (22.7 m³/s) in September 1908 (before irrigation began). During the 2002 fish kill, flows of 475 cubic feet per second (13.5 m³/s) were recorded. During September of the 2001 irrigation shut-off, an average of 688 cubic feet per second (19.5 m³/s) was recorded.
In 2011, the U.S. Environmental Protection Agency (EPA) approve
Klamath River