Permanent settlement of Denver began in 1858 when gold was discovered in small deposits along the South Platte River, near its junction with Cherry Creek. The area attracted prospectors disappointed with the yields at Pike's Peak, as well as gold-seekers newly arrived from the East. By 1867, Denver (named for an early territorial governor, James Denver) had been designated as a territorial capital.

The city's early years were marked by misfortunes that included two major fires, flooding, Indian attacks, and invasion by Confederate forces from Texas during the Civil War (1861–65). Denver also acquired a rather unsavory reputation as new gold discoveries drew a variety of colorful characters to the growing boomtown. However, by 1880, as gold discoveries were waning, gold was replaced by silver as the area's primary source of wealth, and Denver's growth accelerated. The city rebounded from a depression caused by a drop in silver prices in 1893 to become a bustling cosmopolitan center by the late nineteenth century, graced by parks, statues, mansions, and such landmarks as the Tabor Opera House, built by silver baron Horace Tabor. Approximately 30,000 trees were planted along the city's boulevards, and 20,000 acres of land were acquired for its mountain park system. Denver's rapid development and newfound sophistication led to the nickname "Queen City of the Plains."

In the early twentieth century, infrastructure improvements continued, and in 1928, with the opening of the Moffat Tunnel through the Rocky Mountains, the railroad provided a direct connection to the West Coast, spurring additional growth. (The transcontinental line of the Union Pacific Railroad had bypassed Colorado in the nineteenth century, but Denver built a rail line to meet the Union Pacific at Cheyenne, Wyoming.) With a direct link to the West, Denver became a hub for the nation's rail lines and growing highway system. By World War II, the establishment of government agencies including the U.S. Mint and the Bureau of Land Management helped spur a new surge in population, which continued through the 1950s, as the city's climate and recreational opportunities sparked a building boom.

Movement to the suburbs resulted in a drop in population in the 1960s, and the energy crisis of the 1970s also slowed the city's growth. However, urban renewal and a new construction boom, beginning in the late 1970s and continuing through the 1980s and 1990s, have changed the face of the city, giving it a modern, vibrant downtown with 16 skyscrapers constructed during the last decade alone. Denver's downtown is now the nation's tenth largest, and its population is double what it was in 1960. Major improvements continued in the 1990s with the construction of Coors Field, one of the country's top baseball stadiums, and the large, modern Denver International Airport, both of which opened in 1995. The city continues to grow and modernize, with major development planned for the Commons Park area northwest of Union Station—including a series of pedestrian bridges over the South Platte River—and further development in the Golden Triangle district south of Civic Center Park. A major enlargement of the city's convention center is planned as well.