The Great Plains slope gently eastward from the foothills of the Rocky Mts. at an elevation of 6,000 ft (1,829 m) to merge into the interior lowlands at an elevation of roughly 1,500 ft (457 m). The 1,500 ft (457 m) contour line, the 100th meridian of longitude, and the 20-in. (51-cm) isohyet of precipitation are arbitrarily used to mark the region's transitional eastern border. In places, however, it is clearly marked by an escarpment. Much of the Great Plains was once covered by a vast inland sea, and sediments deposited by the sea make up the nearly horizontal rock strata that underlie the area. Intrusive igneous rocks account for sections of higher elevation. The Great Plains region has generally level or rolling terrain; its subdivisions include Edwards Plateau, the Llano Estacado, the High Plains, the Sand Hills, the Badlands, and the Northern Plains.

The Black Hills and several outliers of the Rocky Mts. interrupt the region's undulating profile. The Saskatchewan, Missouri, Platte, Republican, Arkansas, Cimarron, and Canadian rivers flow in wide beds, generally from west to east, and are important sources of water. Rainfall decreases from east to west. Except for its easternmost margin and the elevations, the Great Plains have a semiarid climate, averaging less than 20 in. (51 cm) of precipitation annually. There are wide seasonal temperature ranges and winds of high velocity. In the westernmost sections the chinook, a warm winter wind, brings relief from bitterly cold and snowy winters. The dominant type of vegetation consists of shortgrass prairies; trees grow in moister areas and along water courses.

Although overall the Great Plains are sparsely populated, with much of the grassland devoted to farms and ranches, about half the people live in small to medium-sized urban areas; Edmonton, Alberta and Denver, Colo. are the largest cities in the region. Soils throughout the region are fertile and very productive when water is available. The principal crop is wheat, concentrated in the Spring Wheat Belt (generally N of Nebraska), where the colder climate delays sowing until spring, and the Winter Wheat Belt (centered in Kansas and Oklahoma), where the milder climate allows for winter sowing. Other crops include sorghum, flax, and cotton. Cattle and sheep are raised throughout most of the Great Plains. Oil, natural gas, coal, and gold are among its mineral deposits.

The Great Plains were long inhabited by Native Americans, who hunted the teeming herds of buffalo (see bison) that roamed the grasslands and, due to wholesale slaughter by settlers and the U.S. army, were nearly extinct by the end of the 19th cent. The region was explored by the Spanish in the 17th cent. Until well into the 19th cent., the central Great Plains were called the Great American Desert. The first westward-bound pioneers bypassed the Great Plains. The railroads were largely responsible for their development after the Civil War. An initial wave of settlement was followed by emigration in times of drought. By the mid-1930s, decades of overgrazing and poor soil management in many of the Plains states had resulted in dust storms and the devastation of crops (see Dust Bowl).