Wet bubble disease (WBD) in Agaricus bisporus caused by Mycogone species imposes a substantial economic loss to mushroom production in China. Currently, fungicide application is the main method to control WBD. However, excessive use of fungicides is challenged by the appearance of resistance and food safety. Therefore, it is necessary to explore safe and efficient strategies to control WBD. Strain 9-13, isolated from the rhizosphere soil of Taxus chinensis, showed strong inhibitory activity against three Mycogone species. According to morphological and biochemical characteristics and multilocus phylogenetic analysis, the strain was identified as Streptomyces nojiriensis. In addition, strain 9-13 extracts significantly inhibited mycelial growth and spore germination of M. perniciosa, M. rosea, and M. xinjiangensis in vitro. Strain 9-13 and its extracts also exhibited broad-spectrum antifungal activities against 12 selected plant pathogenic fungi. Scanning electron microscopic observations showed that the extracts destroyed mycelial structure, inducing mycelia to twist and shrink. Moreover, transmission electron microscopy revealed that the extracts resulted in severe plasmolysis, rupture of the cell membrane, and a decrease in cell inclusions, and the cell wall had a rough and uneven surface. Notably, the extracts obviously reduced disease severity and incidence of WBD by from 83.85 to 87.32% in fruiting bodies and 77.36% in mushroom beds and maintained fruiting time and color on harvested mushrooms. Collectively, these results clearly indicate that S. nojiriensis 9-13 is a promising biocontrol agent to control WBD on A. bisporus.