A novel species of powdery mildew, Neoerysiphe sechii sp. nov., has been proposed based on host, morphological characteristics, and gene sequences. The new species was found on chayote (Sechium edule) and a wild species, chayotillo (S. mexicanum), in Veracruz, Mexico. This novel species was identified as a member of Neoerysiphe, based on the morphological characteristics of the anamorph: catenescent conidia, lobed appressoria, and Striatoidium-type conidia. No teleomorph was observed. Neoerysiphe sechii is distinguished by foot cells that are frequently cylindrical with a slight widening at the base, a feature not observed previously in other species in the genus. An Erysiphales-specific primer was designed for the 5′ end of the ITS region of the nuclear rDNA. Independent and concatenated phylogenetic analyses with our rDNA sequences and sequences available in GenBank for Neoerysiphe spp. confirmed that the powdery mildew specimens found in Sechium spp. form an independent and strongly supported lineage. This is the first report of a Neoerysiphe species causing powdery mildew on members of Cucurbitaceae, and it is the second species reported from Mexico after N. cumminsiana. Neoerysiphe sechii is found on cultivated and endemic hosts in Mexico, suggesting that the fungus itself may be endemic.