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Cultivated as a medicinal plant, Cyclocarya paliurus is a monotypic species in its genus and native to China. However, limited information is available regarding diseases that affect its health. In recent years, severe foliar blight and occasional dieback of C. paliurus were observed in the provinces of Anhui, Guangxi, Hubei and Jiangsu in China. The fungus Nigrospora sphaerica was consistently isolated from 70 diseased samples, and its identity was confirmed based on phylogenetic and morphological studies. The phylogenetic analyses of the internal transcribed spacer (ITS) region, translation elongation factor 1-alpha (TEF), and beta-tubulin (TUB) genes compared 15 representative isolates with reference specimens within the Nigrospora genus and validated the identity of the pathogenic fungus. The pathogenicity tests of C. paliurus leaves showed that regardless of whether mycelial plugs or conidial suspensions were used, inoculation with the N. sphaerica isolates resulted in foliar blight symptoms similar to those observed under field conditions. Mycelial growth of N. sphaerica occurred at temperatures ranging from 5 to 35 °C, with an optimum between 25 and 30 °C. In addition, high relative humidity (>85%) could promote conidial germination of N. sphaerica. This study represents an initial step in studying N. sphaerica as a new phytopathogen of C. paliurus in China with the goal of developing efficient control strategies.