The scientists, whose findings were published on Thursday in the journal Science, described clusters of towns and smaller villages connected by complex road networks and housing a society doomed by the arrival of Europeans five centuries ago.
European colonists and the diseases they brought with them probably killed most of the inhabitants, the researchers said. The settlements, consisting of networks of walled towns and smaller villages organized around a central plaza, are now almost entirely overgrown by the forest.
"These are not cities, but this is urbanism, built around towns," University of Florida anthropologist Mike Heckenberger said in a statement.
"If we look at your average medieval town or your average Greek polis, most are about the scale of those we find in this part of the Amazon. Only the ones we find are much more complicated in terms of their planning," Heckenberger added.
Helped by satellite imagery, the researchers spent more than a decade uncovering and mapping the lost communities.
Prior to the arrival of Europeans starting in 1492, the Americas were home to many prosperous and impressive societies and large cities. These findings add to the understanding of the various pre-Columbian civilizations.
The existence of the ancient settlements in the Upper Xingu region of the Amazon in north-central Brazil means what many experts had considered virgin tropical forests were in fact heavily affected by past human activity, the scientists said.
The U.S. and Brazilian scientists worked with a member of the Kuikuro, an indigenous Amazonian people descended from settlements' original inhabitants.