The fern genus Lepisorus represents one of the most complicated and controversial lineages in Polypodiaceae, with about 80 species which have been classified into several separate genera, and is notorious for its taxonomic difficulty. Despite progress in recent phylogenetic studies of the family Polypodiaceae involving Lepisorus and its allies, the deep phylogenetic relationship within this group of ferns is still unresolved, and no formal infrageneric classification has been proposed. This contribution presents the most comprehensive phylogenetic analysis of the genus, with 72% species sampled, using a total-evidence approach based on eight plastid markers and ≤25 morphological characters for each species. The analyses resolve the backbone relationship and yield the most robust phylogenetic framework to date. Congruent with previous studies but with new findings, the results herein show that Lepisorus is monophyletic when Neolepisorus, Lemmaphyllum, Tricholepidium, Neocheiropteris and Lepidomicrosorium are included, as well as Lepisorus jakonensis and Paragramma. Furthermore, 17 well-resolved clades are found in the phylogenetic topology, which can be characterized by morphological synapomorphies from traits of rhizome scales, laminae, sori and paraphyses. Based on molecular and morphological evidence, a new infrageneric classification system of Lepisorus is proposed which subdivided Lepisorus into 17 sections.