AbstractManyDrosophilaspecies differ widely in their distributions and climate niches, making them excellent subjects for evolutionary genomic studies. Here, we have developed a database of high‐quality assemblies for 46Drosophilaspecies and one closely relatedZaprionus. Fifteen of the genomes were newly sequenced, and 20 were improved with additional sequencing. New or improved annotations were generated for all 47 species, assisted by new transcriptomes for 19. Phylogenomic analyses of these data resolved several previously ambiguous relationships, especially in themelanogasterspecies group. However, it also revealed significant phylogenetic incongruence among genes, mainly in the form of incomplete lineage sorting in the subgenusSophophorabut also including asymmetric introgression in the subgenusDrosophila. Using the phylogeny as a framework and taking into account these incongruences, we then screened the data for genome‐wide signals of adaptation to different climatic niches. First, phylostratigraphy revealed relatively high rates of recent novel gene gain in three temperatepseudoobscuraand five desert‐adapted cactophilicmullerisubgroup species. Second, we found differing ratios of nonsynonymous to synonymous substitutions in several hundred orthologues between climate generalists and specialists, with trends for significantly higher ratios for those in tropical and lower ratios for those in temperate‐continental specialists respectively than those in the climate generalists. Finally, resequencing natural populations of 13 species revealed tropics‐restricted species generally had smaller population sizes, lower genome diversity and more deleterious mutations than the more widespread species. We conclude that adaptation to different climates in the genusDrosophilahas been associated with large‐scale and multifaceted genomic changes.