The order Onygenales is classified in the class Eurotiomycetes of the subphylum Pezizomycotina. Families in this order have classically been isolated from soil and dung, and two lineages contain causative agents of superficial, cutaneous and systemic infections in mammals. The ecology and habitat choices of the species are driven mainly by the keratin and cellulose degradation abilities. The present study aimed to investigate whether the ecological trends of the members of Onygenales can be interpreted in an evolutionary sense, linking phylogenetic parameters with habitat preferences, to achieve polyphasic definitions of the main taxonomic groups. Evolutionary processes were estimated by multiple gene genealogies and divergence time analysis. Previously described families, namely, Arthrodermataceae, Ajellomycetaceae, Ascosphaeraceae, Eremascaceae, Gymnoascaceae, Onygenaceae and Spiromastigoidaceae, were accepted in Onygenales, and two new families, Malbrancheaceae and Neogymnomycetaceae, were introduced. A number of species could not be assigned to any of the defined families. Our study provides a revised overview of the main lines of taxonomy of Onygenales, supported by multilocus analyses of ITS, LSU, TUB, TEF1, TEF3, RPB1, RPB2, and ribosomal protein 60S L10 (L1) (RP60S) sequences, combined with available data on ecology, physiology, morphology, and genomics.