This paper reports the largest and most completely resolved phylogenetic tree for mosquitoes ever proposed. Using the framework of relationships supported by data from phylogenomic sampling, we conducted macroevolutionary tests to demonstrate that the origin and diversification of mosquito lineages was broadly contemporaneous with their hosts and was influenced by major geologic events. Several distinct lineages of mosquitoes are together among the most important disease vectors on earth and our results show that prior to their impact on human health, and throughout earth history, mosquitoes experienced multiple periods of diversification and host expansion.