White entry into the Uaupés area began in the 1730s, when Portuguese troops were dispatched as far as its headwaters. Despite Portugal's official abolition of slavery in 1750, 20,000 Indians from the upper Rio Negro were enslaved between 1740 and 1750.
During the latter half of the eighteenth century, the Portuguese established a military outpost at the confluence of the Uaupés and Rio Negro and sent reconnaissance expeditions into the Uaupés Basin. The Portuguese resettled Indians at forts, where labor was needed to grow crops, manufacture goods, and demarcate borders. The Indians often resented and resisted such policies: in 1782 and 1783 Indians resisting resettlement deserted many settlements on the lower Uaupés.
In 1849 the Mission of the Uaupés and Içana was founded, with a missionary appointed to populations on the Rio Uaupés. In the 1880s the provincial government invited the Franciscans into the area, and in 1914 Pope Pius X conferred upon the Salesian order the administration of Rio Negro Prefecture. In 1929 the Salesians founded a mission station 60 kilometers south of the Wanano area.
Commercial rubber collection reached the periphery of the Wanano area between 1880 and 1912; it was briefly revived during World War II. Many Wanano emigrated when demand for rubber provided wages in Colombia and the lower Rio Negro. Opportunities for wage labor continue to draw indigenous peoples out of the region, despite the poor living conditions that generally accompany employment.