BACKGROUND: We evaluate the process by which the Americas were originally colonized and propose a three-stage model that integrates current genetic, archaeological, geological, and paleoecological data. Specifically, we analyze mitochondrial and nuclear genetic data by using complementary coalescent models of demographic history and incorporating non-genetic data to enhance the anthropological relevance of the analysis. METHODOLOGY/FINDINGS: Bayesian skyline plots, which provide dynamic representations of population size changes over time, indicate that Amerinds went through two stages of growth approximately 40,000 and approximately 15,000 years ago separated by a long period of population stability. Isolation-with-migration coalescent analyses, which utilize data from sister populations to estimate a divergence date and founder population sizes, suggest an Amerind population expansion starting approximately 15,000 years ago. CONCLUSIONS/SIGNIFICANCE: These results support a model for the peopling of the New World in which Amerind ancestors diverged from the Asian gene pool prior to 40,000 years ago and experienced a gradual population expansion as they moved into Beringia. After a long period of little change in population size in greater Beringia, Amerinds rapidly expanded into the Americas approximately 15,000 years ago either through an interior ice-free corridor or along the coast. This rapid colonization of the New World was achieved by a founder group with an effective population size of approximately 1,000-5,400 individuals. Our model presents a detailed scenario for the timing and scale of the initial migration to the Americas, substantially refines the estimate of New World founders, and provides a unified theory for testing with future datasets and analytic methods.