Here, we present the newly identified Inosperma macrocarpa and the first record of I. afromelliolens from West Africa. Inosperma macrocarpa is nested in an Old World Tropical clade, based on a molecular phylogeny inferred from the sequences of ITS, LSU, RPB2, and TEF1. Complete descriptions and illustrations, including photographs and line drawings, of the new species are presented. Morphological and molecular analyses based on collections from Benin confirmed the presence of I. afromelliolens in West Africa. Toxicity analysis showed that neither species contained muscarine, which further supports the hypothesis that the ability to produce muscarine is a derived trait of Inosperma.