The Tibetan Plateau is the highest and one of the most demanding environments ever inhabited by humans. We investigated the timing and mechanisms of its initial colonization at the Nwya Devu site, located nearly 4600 meters above sea level. This site, dating from 40,000 to 30,000 years ago, is the highest Paleolithic archaeological site yet identified globally. Nwya Devu has yielded an abundant blade tool assemblage, indicating hitherto-unknown capacities for the survival of modern humans who camped in this environment. This site deepens the history of the peopling of the “roof of the world” and the antiquity of human high-altitude occupations more generally.