A series of N-aryl-pyridine-4-one derivatives were designed and synthesized using maltol and antidesmone as lead compounds, and then their fungicidal/bactericidal activities and possible mechanism of action against Colletotrichum musaewere explored. Most of these compounds exhibited significant fungicidal activity in vitro. Especially, compound 23has more than 90% inhibitory activity against nine plant pathogenic fungi at 50 μg mL–1, which is superior to azoxystrobin. Moreover, an in vivobioassay also demonstrated that compound 23exhibited high-efficiency broad-spectrum antifungal activity and can effectively control postharvest diseases of mango. In addition, it was found that compounds 22and 23can also effectively control rice bacterial leaf blight in pot experiments, which was even more effective than zhongshengmycin. Preliminary mechanism studies revealed that compound 23may cause cell membrane and mitochondria destruction. These findings indicate that compound 23can be used to develop potential agrochemical fungicides and bactericides.