The cultivation and overall quality of Litchi, a fruit of significant commercial value in China, are hindered by the presence of the oomycetes pathogen Peronophythora litchii. This pathogen is responsible for the occurrence of litchi downy blight, resulting in substantial economic losses during the storage and transportation of the fruit, and affects nutritional growth. Effective and environmentally safe methods to control litchi downy blight are urgently needed. The application of biocontrol agents such as Streptomyces bacteria has proven effective for controlling plant diseases. Our present study isolated the Streptomyces strain TJGA-19, identified as S. abikoensis, with potent inhibitory activity against P. litchii. The antifungal active substances are mainly in the aqueous phase of TJGA-19 fermentation filtrate extraction. The fermentation filtrate of TJGA-19 not only suppressed the pathogen growth, sporulation, and sporangia germination, but also delayed the disease development of litchi downy blight. In addition, the stability of the TJGA-19 fermentation filtrate was not sensitive to the proteinase K, temperature, white-flourescence light, or ultraviolet treatment. Furthermore, the morphology and ultrastructure of P. litchii treated with fermentation filtrate was characterized by marked shrinking and deformation, with serious disruption of plasma membrane permeabilization and the organelles. Hence, S. abikoensis TJGA-19 and its metabolites demonstrated marked efficiency against the phytopathogenic pathogen P. litchii and provide a potential candidate for controlling litchi downy blight.