Some present-day humans derive up to ∼5% 1 of their ancestry from archaic Denisovans, an even larger proportion than the ∼2% from Neanderthals 2. We developed methods that can disambiguate the locations of segments of Denisovan and Neanderthal ancestry in present-day humans and applied them to 257 high-coverage genomes from 120 diverse populations, among which were 20 individual Oceanians with high Denisovan ancestry 3. In Oceanians, the average size of Denisovan fragments is larger than Neanderthal fragments, implying a more recent average date of Denisovan admixture in the history of these populations (p = 0.00004). We document more Denisovan ancestry in South Asia than is expected based on existing models of history, reflecting a previously undocumented mixture related to archaic humans (p = 0.0013). Denisovan ancestry, just like Neanderthal ancestry, has been deleterious on a modern human genetic background, as reflected by its depletion near genes. Finally, the reduction of both archaic ancestries is especially pronounced on chromosome X and near genes more highly expressed in testes than other tissues (p = 1.2 × 10−7 to 3.2 × 10−7 for Denisovan and 2.2 × 10−3 to 2.9 × 10−3 for Neanderthal ancestry even after controlling for differences in level of selective constraint across gene classes). This suggests that reduced male fertility may be a general feature of mixtures of human populations diverged by >500,000 years. •Denisovan admixture into modern humans occurred after Neanderthal admixture•There is more Denisovan ancestry in South Asians than expected from current models•Denisovan ancestry has been subject to positive and negative selection after admixture•Male infertility most likely occurred after modern human interbreeding with Denisovans Sankararaman et al. present a map of Denisovan and Neanderthal ancestry in 120 diverse populations and show that Denisovan admixture post-dated Neanderthal admixture. South Asians have more Denisovan ancestry than expected. There was selection both for and against archaic ancestry. Hybridization with Denisovans was probably associated with reduced male fertility.