The Snake River is a major river in the interior Pacific Northwest region of the United States. About 1,080 miles (1,740 km) long, it is the largest tributary of the Columbia River, which is the largest North American river that empties into the Pacific Ocean. Beginning in Yellowstone National Park, western Wyoming, it flows across the arid Snake River Plain of southern Idaho, the rugged Hells Canyon on the borders of Idaho, Oregon and Washington, and finally the rolling Palouse Hills of southeast Washington. It joins the Columbia River just downstream from the Tri-Cities, Washington, in the southern Columbia Basin.

The river's watershed, which drains parts of six U.S. states, is situated between the Rocky Mountains to the north and east, the Great Basin to the south, and the Blue Mountains and Oregon high desert to the west. The region has a long history of volcanism; millions of years ago, Columbia River basalts covered vast areas of the western Snake River watershed, while the Snake River Plain was a product of the Yellowstone volcanic hotspot. The river was further altered by catastrophic flooding in the most recent Ice Age, which created such features as the Snake River Canyon and Shoshone Falls.

The Snake River once hosted some of the largest North American runs of salmon and other anadromous fish. For thousands of years, salmon fishing has played a central role in the culture and diet of indigenous peoples. The Shoshone and Nez Perce were the largest of several tribes that lived along the river by the turn of the 19th century. In 1805, while searching for a route from the eastern US to the Pacific, Lewis and Clark became the first non-natives to see the river. Fur trappers explored more of the watershed, and drove beaver to near extinction as the Americans and British vied for control of Oregon Territory.

Although travelers on the Oregon Trail initially shunned the dry and rocky Snake River region, a flood of settlers followed gold discoveries in the 1860s, leading to decades of military conflict and the eventual expulsion of tribes to reservations. At the turn of the 20th century, some of the first large irrigation projects in the western US were developed along the Snake River. South-central Idaho earned the nickname "Magic Valley" with the rapid transformation of desert into farmland. Numerous hydroelectric dams were also constructed, and four navigation dams on its lower section created a shipping channel to Lewiston, Idaho – the furthest inland seaport on the West Coast.

While dam construction, commercial fishing and other human activities have greatly reduced anadromous fish populations since the late 19th century, the Snake River watershed is still considered important habitat for these fish. The Snake and its tributary, the Salmon River, host the longest sockeye salmon run in the world, stretching 900 miles (1,400 km) from the Pacific to Redfish Lake in Idaho. Since the 1950s, public agencies, tribal governments and private utilities have invested heavily in fishery restoration and hatchery programs, with limited success. The proposed removal of the four lower Snake River dams for fish passage is a significant ongoing policy debate in the Pacific Northwest.

The Snake River starts to the north of Two Ocean Pass near the southern border of Yellowstone National Park, about 9,200 feet (2,800 m) above sea level in the Rocky Mountains of Wyoming. The river descends west through the high mountains of the Teton Wilderness meeting the Lewis River and continuing south into Jackson Lake in Grand Teton National Park, a natural glacial lake enlarged by Jackson Lake Dam. Joined by Pacific Creek and Buffalo Fork below the dam, it meanders southward through the alpine valley of Jackson Hole situated on the plain in front of the Teton Range to the west and the Gros Ventre Range to the east.

Below the town of Jackson it forms the Snake River Canyon of Wyoming, turns west and crosses into Idaho, where the Palisades Dam forms Palisades Reservoir. From there it flows northwest through Swan Valley to join the Henrys Fork on an alluvial plain near Rexburg. The Henrys Fork is sometimes called the "North Fork" of the Snake River, while the section of the main Snake River above their confluence is sometimes called the "South Fork".

Turning southwest, the river begins its long journey across the Snake River Plain, passing through Idaho Falls and receiving the Blackfoot River from the left before entering the 20-mile (32 km)-long American Falls Reservoir, formed by American Falls Dam. From American Falls it turns west, flowing through Minidoka Dam and Milner Dam, where large volumes of water are diverted for irrigation. Below Milner Dam it enters the Snake River Canyon of Idaho, where the river narrows, forming rapids and waterfalls. In the 70-mile (110 km) stretch between Milner Dam and the confluence with the Malad River near Hagerman Fossil Beds National Monument, the Snake River descends a total of 1,300 feet (400 m) over a series of cataracts and rapids, chief of which include Caldron Linn, Twin, Shoshone, Pillar, Auger, and Salmon Falls. Idaho Power operates several small hydroelectric plants along this stretch of the river. The largest single drop is 212-foot (65 m) Shoshone Falls, which in the spring flows with such force that 19th-century writers called it the "Niagara of the West".