The Snake is a major river in the greater Pacific Northwest region of the United States. It is the largest and longest tributary of the Columbia River, which is the largest North American river that empties into the Pacific Ocean. Rising in western Wyoming, the river flows westwards through the Snake River Plain, and turns north to empty into the Columbia at the Tri-Cities area of the state of Washington, draining 108,000 square miles (280,000 km2) in parts of six U.S. states.

Formed by the confluence of three tiny headstreams on the southwest flank of Two Oceans Plateau in western Wyoming and Yellowstone National Park, the Snake starts out as a small river flowing west and south into Jackson Lake. Its first 50 miles (80 km) run through the valley of Jackson Hole, which cuts between the Teton Range and the Continental Divide. The Snake takes a large bend northwest through Snake River Canyon, cutting through the Teton Range and into eastern Idaho, receiving first the Greys River before entering Palisades Reservoir where it is also met by the Salt River at the mouth of Star Valley. After passing through Palisades Dam, the Snake River empties onto the Snake River Plain, a vast physiographic province extending through southern Idaho across the massif of the Rocky Mountains and underlain by the Snake River Aquifer, one of the most productive aquifers in the United States.

Southwest of the city of Rexburg, the Snake receives from the right the Henrys Fork, sometimes called the North Fork of the Snake River. The confluence with the Henrys Fork takes the river southwards through downtown Idaho Falls, rounding the Fort Hall Indian Reservation and into American Falls Reservoir, receiving the Portneuf River. The Portneuf River valley is an overflow channel that in the last glacial period carried floodwaters from pluvial Lake Bonneville into the Snake River Plain, carving out many topographic features and significantly altering the Snake River landscape. The Snake River resumes its journey westwards, then enters the Snake River Canyon of Idaho, where it drops over Shoshone Falls, a waterfall that marks the historical upriver limit of migrating salmon, and passing under the Perrine Bridge. Close to Twin Falls, the Snake approaches the southernmost point in its entire course, after which it starts to flow generally northwest.

Shortly after it passes within 30 miles (48 km) of the Idaho state capital of Boise, the river surges past the state border into Oregon, close to where it meets the Owyhee River, Boise River and Payette River. The Snake River then begins to define the roughly 200-mile (320 km)-long Idaho-Oregon state border, which follows the river into Hells Canyon, a steep and spectacular gorge that cuts through the Salmon River Mountains and Blue Mountains of Idaho and Oregon. Hells Canyon is one of the most rugged and treacherous portions of the course of the Snake River, which pioneers on the Oregon Trail and steamboat operators in the 19th century had great difficulty negotiating. There were hundreds of rapids in Hells Canyon, some of which have been stilled by the three dams of the Hells Canyon Hydroelectric Project: Hells Canyon, Oxbow, and Brownlee.

The Salmon River, the largest tributary of the Snake River, meets the river in one of the remotest areas of its entire course, nearly at the halfway point in Hells Canyon. From there, the Snake crosses into Washington and Idaho, receiving the Grande Ronde River from the west before receiving the Clearwater River at Lewiston, the uppermost major city on the navigable stretch of the Snake. As the Snake leaves Hells Canyon and spreads into the low-lying Palouse Hills of eastern Washington, the Lower Snake River Project's four dams have transformed the Snake River into a series of reservoirs. The confluence of the Snake and Columbia Rivers has been submerged in Lake Wallula, the reservoir of McNary Dam. The Columbia River flows about 320 miles (510 km) further to the Pacific Ocean, cutting through the Cascade Range via the Columbia River Gorge.

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