Phthalide, benzoxazole, and chromene are important heterocyclic skeletons with extensive biological activities. In order to develop novel potential antifungal agents, twenty-two benzoxazole/chromene-containing phthalide derivatives were prepared, and their fungicidal activity against nine common plants pathogenic fungi were evaluated in vitro. The EC 50 values indicated that compound Z-4b displayed superior antifungal activity against P. oryzae (11.0 μg/mL), F. solani (8.5 μg/mL), P. capsici (27.8 μg/mL), V. mali (3.1 μg/mL) and A. brassicae (4.3 μg/mL) strains, which was more potent than the two commercialized fungicides hymexazol and chlorothalonil. In addition, the structure-activity relationship analysis demonstrated that the combination site of oxazolamide with phthalide has an important effect on antifungal activity. This research offers a potential compound for the development of novel agricultural fungicides.