Among the Native American tribes who lived in what is now Colorado were the Apache, Arapaho, Cheyenne, Comanche, Kiowa, Navajo, Pueblo, Shoshone, and Ute. They built on their ancestors of the Plains Woodland and Basket Makers cultures. Another well-known native people were the Anasazi, who carved dwellings out of cliff faces; some of these can be seen even today.

As in several neighboring states, the Spanish explorer Francisco de Coronado rolled through what is now Colorado in 1541. He was on the hunt for some legendary deposits of gold. Finding no joy in Colorado, he moved on.

Another European explorer, René-Robert Cavelier, Sieur de La Salle, traveled down the Mississippi River in 1682 and set foot in eastern Colorado, claiming that land, the river, and everywhere the river drained for his king, Louis XIV of France. This French claim held until Great Britain's victory over France in the French and Indian War; then, Spain took over what La Salle had referred to as La Louisiane.

France retained control of the Louisiana Territory in 1800 and then, in 1803, sold it to the United States as the Louisiana Purchase. The one exception to this was part of western Colorado, which remained in Spanish hands.

The well-known explorer Zebulon Pike (left) traveled through Colorado in 1806, mapping as he went. He found a very tall mountain (14,110 feet high) peak, which came to be known as Pike's Peak. Other explorers–including "The Pathfinder," John C. Fremont–followed. Other Americans followed, pursuing the burgeoning fur trade. The opening of the Santa Fe Trail in 1821 brought many settlers through Colorado on their way to what became New Mexico; some of these travelers stayed in Colorado, liking what they saw there. Fort Bent, Colorado's first permanent American settlement, came along in 1833 and was built along the Santa Fe Trail.

Part of Colorado was briefly part of the territory claimed by Texas, after it declared its independence from Mexico in 1835 and before it became a state in 1845.

The United States and Mexico fought a war in 1846–1848. The American victory resulted in the Mexican Cession, a large area of land the ownership of which changed from Mexico to the U.S. This included a bit of what is now western Colorado.

The present borders of the State of Colorado include several strips of land that was, at various times in the 1850s, part of the the Kansas Territory, the Colorado Territory, the New Mexico Territory, and the Utah Territory.

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