Polygonatum odoratum (Mill.) Druce has been widely used in traditional Chinese medicines owing to its renown antioxidant, anticancer, and antidiabetic properties. During surveys conducted in the Zhijin County, Bijie City, Guizhou Province in China, prominent yellow-brown spots were observed on the leaves of P. odoratum. These spots eventually led to the death of the entire plant as they expanded, thus affecting the yield and quality of P . odoratum. In this study, infected P . odoratum leaves were collected and, based on morphological characteristics and multi-locus sequence typing (MLST) (actin, glyceraldehyde-3-phosphate dehydrogenase, beta-tubulin, and the internal transcribed spacer region of rDNA), Colletotrichum camalliae Massee was isolated and identified as the causal agent of the disease. This is the first study to investigate P . odoratum leaf infection by C . camelliae and is therefore, of great significance for this popular and highly valued medicinal plant; furthermore, it provides a sound theoretical basis for targeted control of the leaf spot disease.