Population genetic statistics from multilocus genotype data inform our understanding of the patterns of genetic variation and their implications for evolutionary studies, generally, and human disease studies in particular. In any given population one can estimate haplotype frequencies, identify deviation from Hardy–Weinberg equilibrium, test for balancing or directional selection, and investigate patterns of linkage disequilibrium. Existing software packages are oriented primarily toward the computation of such statistics on a population-by-population basis, not on comparisons among populations and across different statistics. We developed PyPop (Python for Population Genomics) to facilitate the analyses of population genetic statistics across populations and the relationships among different statistics within and across populations. PyPop is an open-source framework for performing large-scale population genetic analyses on multilocus genotype data. It computes the statistics described above, among others. PyPop deploys a standard Extensible Markup Language (XML) output format and can integrate the results of multiple analyses on various populations that were performed at different times into a common output format that can be read into a spreadsheet. The XML output format allows PyPop to be embedded as part of a larger analysis pipeline. Originally developed to analyze the highly polymorphic genetic data of the human leukocyte antigen region of the human genome, PyPop has applicability to any kind of multilocus genetic data. It is the primary analysis platform for analyzing data collected for the Anthropological component of the 13th and 14th International Histocompatibility Workshops. PyPop has also been successfully used in studies by our group, with collaborators, and in publications by several independent research teams.