New Mydidae species are described from the Afrotropical and Oriental regions including the first records of this family from several countries in eastern Africa (Kenya, Tanzania, and Uganda) and Mauritania in western Africa as well as Nepal and Thailand in Asia. The new species are, Leptomydinae: Leptomydas notossp. n. (south-western India), Leptomydas raptisp. n. (south-central Nepal), Leptomydas tigrissp. n. (north-central Thailand); Syllegomydinae: Mydaselpidini: Mydaselpis ngurumanisp. n. (south-eastern Kenya, north-eastern Tanzania), Vespiodes phaiossp. n. (south-eastern Kenya); Syllegomydinae: Syllegomydini: Syllegomydas (Notobates) astrictussp. n. (Kenya), Syllegomydas (Notobates) heothinossp. n. (Kenya and Uganda), Syllegomydas (Syllegomydas) elachyssp. n. (northern Zimbabwe). Syllegomydas (Syllegomydas) proximus Séguy, 1928 is recorded from western Mauritania and re-described. Syllegomydas (Notobates) dispar (Loew, 1852), which was previously listed as incertae sedis in the Afrotropical Diptera catalogue, is re-described and illustrated based on examination of the type specimens and several additional specimens from Mozambique. Cephalocera annulata Brunetti, 1912 and Syllegomydas bucciferus Séguy, 1928, described from north-eastern India and previously unplaced in the Oriental Diptera catalogue, are newly combined with Leptomydas Gerstaecker, 1868 and together with Leptomydas indianus Brunetti, 1912, also from north-eastern India, placed in Leptomydinae. Comments on the possible synonymy of the genera of Mydaselpidini are made. Illustrations and photographs are provided to support the descriptions and future identification. A provisional dichotomous key to Mydidae genera occurring in eastern Africa (Kenya, Malawi, Mozambique, Somalia, Tanzania, Uganda) and the Oriental Region is provided. Distribution, occurrence in biodiversity hotspots and high-biodiversity wilderness areas, and seasonal incidence are discussed for all species.