Some 3 mln years ago, the genus Homo originated from australopithecines in Africa. In the Pleistocene, in the course of subsequent evolutionary processes such as natural selection, hybridization, and adaptation to changing environments, in the 200–100 ka BP interval, anatomically modern humans emerged in Africa, H. sapiens neanderthalensis in Europe, and H. sapiens denisovan in Central and Northern Asia. The origin of these taxa has been discussed in various publications and at many symposia. In the course of debates, several hypotheses were advanced—African Eve, multiregional evolution, evolution with hybridization, etc. All of them proceed from the assumption that the earliest anatomically modern humans originated in Africa. The main disagreement between the experts concerns the role of native Eurasians in the origin of H. sapiens sapiens following the migration of anatomically modern humans from Africa to Eurasia. In several publications of mine, a scenario of the phylogenetic history of the genus Homo, somewhat different from the currently discussed hypotheses, was proposed. The analysis of the genetic legacy of anatomically modern humans, H. sapiens neanderthalensis, and H. sapiens denisovan has shown that those hominins were able to hybridize and that the hybrids were fertile. This means that hybridization and assimilation proceeded not between separate species but within a single species, whose populations were open genetic systems. Consequently, if, at the final stage of the phylogenetic history of Homo, 200–100 ka BP, three taxa capable of hybridization emerged on various continents in the process of a long evolution, then all previous Early and Middle Pleistocene taxa in Africa, Europe, and Asia, established by the analysis of fossils, had likewise open genetic systems. This means that over a nearly 3 mln year long evolution of the genus Homo, resulting in progressive sapienization, three key factors—natural selection, hybridization, and adaptation to changing environments of the Pleistocene—have shaped both morphology and genetics of that genus. The article addresses the origin of a single basal species in Africa, ancestral to all anatomically modern humans, their spread to Eurasia, and role in the origin of H. sapiens neanderthalensis in Europe.