The city of San Carlos de R�o Negro was founded in 1759 as a camp setup by the expedition captained by Jos� Solano y Bote. The expedition moved into the area to explore the extent of the limits of exploration as defined by the Treaty of Madrid between the Crowns of Portugal and Spain. Jos� Solano y Bote set up his exploration base there on the banks of the Rio Negro with the few men that had survived the trek up the Orinoco River. Most of the men that accompanied the expedition, including the famous Swedish botanist Pehr L�fling, succumbed to tropical diseases, especially yellow fever.
In May 1800, the explorers Alexander von Humboldt and Aim� Bonpland visited the town, constituting the southernmost point of their expedition of the Amazon Basin
