The Auke Tlingit had fish camps at the mouths of the streams that are now part of the City and Borough of Juneau. In 1880, nearly twenty years before the Klondike gold discovery, Auke Chief Kowee led Joe Juneau and Richard Harris to Gold Creek where they found gold. A camp quickly was established that became the town of Juneau. Hard rock gold was found across the channel in 1882, and the Treadwell Mine employed 2,000 people, and produced $66 million in gold in its 35 years of operation. More hard rock discoveries followed, and the Alaska-Juneau Mine on the mainland became the largest of its kind in the world, producing over $80 million in gold before it closed in 1944.

Juneau quickly became larger than Sitka and advocated to become Alaska's political center. The City of Juneau was one of the first to incorporate after Congress passed legislation in 1900. The legislation called for the government offices to move from Sitka to Juneau, but the physical move did not happen until 1906. The acts that made Alaska a territory in 1912 and a state in 1959 named Juneau as the capital. After Congress created the Tongass National Forest in 1909, the Forest Service established its regional office at Juneau and much surrounding land became part of the forest, including Mendenhall Glacier, already a popular visitor attraction.

Along with mining and government, fishing, a sawmill, trading, professional services, and tourism helped Juneau be Alaskas largest city in population between 1910 and 1950. The geography offered little flat land, so mine tailings were used to make level areas along the waterfront for buildings. Native people continued to live near the mouth of Gold Creek. Juneau and Douglas became home to Japanese, Filipinos, and other Asian-Americans who worked in the fisheries and opened small businesses.

After Alaska became a state in 1959, a number of new government buildings for federal, state, and city offices were built. Along with government, Juneau is a major destination on Alaskas scenic Inside Passage for cruise ships five months of the year. In 1970 the City of Juneau, City of Douglas, and Greater Juneau Borough unified as the City and Borough of Juneau. The community was one of the first to see potential historic districts with its downtown business district and earliest neighborhoods.