The river system originates in the Andes Mountains of Peru and travels through Ecuador, Colombia, Venezuela, Bolivia, and Brazil before emptying into the Atlantic Ocean. Roughly two-thirds of the Amazon's main stream is within Brazil.

Brazil is the country that contains the vast majority of the Amazon River and its surrounding basin. Approximately 60% to 64% of the Amazon rainforest and the main stem of the river are located within Brazilian borders. The river originates in the Andes Mountains of Peru (which holds the second-largest portion, at about 13-16%) and flows eastward across the continent before emptying into the Atlantic Ocean on the northeastern coast of Brazil. Other countries that share the Amazon basin include Colombia, Bolivia, Venezuela, Ecuador, Guyana, Suriname, and French Guiana, but their shares are significantly smaller, ranging from less than 1% to about 10%. Brazil's dominance over the river system makes it the central player in international discussions regarding the environmental conservation of the "lungs of the planet." Major Brazilian cities like Manaus serve as the primary hubs for river commerce and tourism. Because such a massive portion of the river's navigable length is in Brazil, the country's infrastructure, including dams and shipping lanes, has a profound impact on the entire transboundary river system's health and flow.