The Columbia River, Klamath River in Northern California, Pit River in Northern California, and Fraser River in Southern British Columbia are the only four rivers connecting the east-side watersheds of the Cascade Mountain Range to the Pacific Ocean. Each river has created a gorge through the Cascade Mountain Range. The Columbia River Gorge marks the state line between Oregon and Washington. The wide range of elevation and precipitation makes the Columbia River Gorge an extremely diverse and dynamic place. Ranging from 4,000 feet (1,200 m) to sea level, and transitioning from 100 inches (2,500 mm) of precipitation to only 10 inches (250 mm) in 80 miles (130 km), the Gorge creates a diverse collection of ecosystems from the temperate rain forest on the western end—with an average annual precipitation of 75 to 100 inches (1,900 to 2,500 mm)—to the eastern grasslands with average annual precipitation between 10 and 15 inches (250 and 380 mm), to a transitional dry woodland between Hood River and The Dalles.[citation needed] Isolated micro-habitats have allowed for many species of endemic plants and animals to prosper, including at least 13 endemic wildflowers.

The Gorge transitions between temperate rainforest to dry grasslands in only 80 miles, hosting a dramatic change in scenery while driving down Interstate 84. In the western, temperate rainforest areas, forests are marked by big-leaf maples, Douglas fir, and Western hemlock, all covered in epiphytes. In the transition zone (between Hood River and The Dalles), vegetation turns to Oregon white oak, Ponderosa pine, and cottonwood. At the eastern end, the forests make way for expansive grasslands, with occasional pockets of lodgepole and Ponderosa pine.

The gorge has supported human habitation for over 13,000 years. Evidence of the Folsom and Marmes people, who crossed the Bering land bridge from Asia, were found in archaeological digs. Excavations near Celilo Falls, a few miles east of The Dalles, show humans have occupied this salmon-fishing site for more than 10,000 years.

Prior to the construction of the Barlow Road, the only practical option for many immigrants to the Willamette Valley along the Oregon Trail was to convert their wagons into rafts at the Dalles. Many died or lost their possessions in the attempt to convey their wagons via rafts through the Cascade Rapids.

The gorge has provided a transportation corridor for thousands of years. Native Americans would travel through the Gorge to trade at Celilo Falls, both along the river and over Lolo Pass on the north side of Mount Hood. In 1805, the route was used by the Lewis and Clark Expedition to reach the Pacific. Early European and American settlers subsequently established steamboat lines and railroads through the gorge. Today, the BNSF Railway runs freights along the Washington side of the river, while its rival, the Union Pacific Railroad, runs freights along the Oregon shore. Until 1997, Amtrak's Pioneer also used the Union Pacific tracks. The Portland segment of the Empire Builder uses the BNSF tracks that pass through the gorge.

The Columbia River Highway, built in the early 20th century, was the first major paved highway in the Pacific Northwest. Shipping was greatly simplified after Bonneville Damand The Dalles Dam submerged the gorge's major rapids such as Celilo Falls, a major salmon fishing site for local Native Americans until the site's submergence in 1957.

In November 1986, Congress made it the second U.S. National Scenic Area and established the Columbia River Gorge Commission as part of an interstate compact. The experimental designation came in lieu of being recognized as a national park, which would require the existing industries in towns along the river to relocate. The designation was initially opposed by residents fearing government encroachment, due to restrictions from the plan like building paint colors, and conservationists who feared additional development in the region. In 2004, the gorge became the namesake of the Columbia Gorge American Viticultural Area, a 4,432-acre (1,794 ha) area located on both sides of the river.