Based on the most comprehensive molecular phylogeny to date, this study traces the evolution of louse flies and bat flies from their origin shortly after the Cretaceous–Paleogene (K–Pg) boundary. The bird-parasitic genus Ornithoica Rondani was recovered as the sister group to all other louse flies, supporting the hypothesis of a bird-parasitic ancestor for the group. Louse fly parasites of marsupials and placental mammals evolved through repeated host shifts from bird-parasitizing ancestors. Bat flies are strongly supported as the sister clade to louse flies and underwent a major divergence into Western and Eastern Hemisphere radiations. Within bat flies, the bot-producing Ascodipterinae form the sister group to the wingless Nycteribiinae, rendering the traditional Streblidae paraphyletic. A revised classification of Hippoboscidae is proposed, with 2 subfamilies—Hippoboscinae (louse flies) and Nycteribiinae (bat flies)—each containing 4 tribes. To ensure generic monophyly, the following synonymies are established: Melophagus Latreille, 1802 as senior synonym of Lipoptena Nitzsch, 1818, syn. n., Ornithomya Latreille, 1802 as senior synonym of Crataerina Olfers, 1816, syn. n., Trichobius Gervais, 1844 as senior synonym of Aspidoptera Coquillett, 1899, syn. n., and Brachytarsina Macquart, 1851 as senior synonym of Megastrebla Maa, 1971, syn. n.
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