The first European settlement on the site was a small fort (São José do Rio Negrinho) built in 1669 by Captain Francisco da Motta Falcão. The mission and village that later grew up were called Villa da Barra, or Barra do Rio Negro (barra referring to the sandbar at the mouth of the Negro). The town succeeded Barcelos in 1809 as capital of the Rio Negro captaincy general and in 1850 became the capital of Amazonas province (later state). Its name was then changed to Manáos (after an Indian river tribe); since 1939 it has been spelled Manaus. From 1890 to 1920 a regional economic boom based on the production of natural rubber from the tree Hevea brasiliensis brought prosperity to the city. Manaus's majestic buildings and homes, including the cathedral and ornate opera house (Teatro Amazonas, constructed 1896 and renovated 1987–90), and the creation of port commerce date from that period. Manaus also became one of the first cities in Brazil to have electricity. It was made an episcopal see in 1892. In 1902 a British corporation began improvements to the port facilities, including a customs house, a stone quay, storehouses, and floating wharves to allow for the annual rise and fall (up to 40 feet 【12 metres】) of the river. Most of the iron, glass, and other building materials were specially ordered from Britain, France, and elsewhere in Europe. Manaus declined in the 1920s, when the price of natural rubber collapsed on the world market. Although its economy strengthened somewhat during World War II, Manaus did not prosper significantly until after it was declared a duty-free zone in 1967.

Manaus is now a major inland port reached by oceangoing vessels from the Atlantic and is the chief collecting and distribution centre for the riverine areas of the entire upper Amazon basin. In the late 1970s the Brazilian government and private companies began extensive deforestation to develop the mineral and agricultural wealth of the surrounding forested region. The government also installed a fishing terminal in Manaus. The city receives beef from the savannas of the upper Branco River, which also supply hides for export. Manaus's industries include brewing, shipbuilding, soap manufacturing, the production of chemicals, the manufacture of electronics equipment, and petroleum refining (the oil being brought by barge down the Amazon from Peru). The scales of the pirarucu (Arapaima gigas), a large South American fish, are exported for use as nail files. The city's principal exports include electrical equipment, petroleum, chemicals, Brazil nuts, and a host of minor forest products. Tourism has become a growing part of the economy.

Manaus has botanical and zoological gardens, and there is a natural jungle park on its outskirts. It is the seat of the National Research Institute of Amazonia (founded 1954), the University of Amazonas (1962), the Geographic and Historical Institute of Amazonas (1917), and a Salesian school for orphans. The city has an international airport. Manaus contains half of the state's population and rivals Belém (near the Atlantic Ocean) as the Amazon basin's largest urban centre. Pop. (2005 est.) 1,634,100.