Ancient Brazilian genomes show strong Australasian signal indicating Denisovan ancestry. Denisovan DNA persisted in Uruguay individual only 1,500 years old from massive admixture. Admixture happened around 40,000 years ago before Americas settlement. Stronger Denisovan signal in ancient Uruguay and Panama than Brazil genomes. Multiple migration waves along Atlantic coast from Panama. Distinct genetic links between Mesoamerica and South American ancients. Paleolithic humans entered Americas 26,000-19,000 years ago via Siberia-Alaska bridge. Only 12 ancient South American whole genomes sequenced so far. Warmer climates hindered ancient DNA recovery until now. Denisovans related to Neanderthals from Siberian and Tibetan specimens. Australasian signal supports coastal migration route.