Abstract <p>Herein, a series of novel 4-chromanone-derived compounds containing carboxamide and oxime ether moieties were synthesized, and their structures were fully characterized by ¹H, ¹³C NMR, and HRMS. Subsequently, the in vitro antibacterial activities of these target compounds against <i>Xanthomonas oryzae pv. oryzae</i> (<i>Xoo</i>)<i>, Xanthomonas axonopodis</i> pv. <i>citri</i> (<i>Xac</i>), and <i>Pseudomonas syringae</i> pv. <i>actinidiae</i> (<i>Psa</i>), as well as their in vitro antifungal activities against <i>Fusarium equiseti (Corda) Sacc.</i> (<i>F. equiseti</i>), <i>Gibperella zeae</i> (<i>G. zeae</i>), <i>Sclerotinia sclerotiorum</i> (<i>S. sclerotiorum</i>), <i>Botrytis cinerea</i> (<i>B. cinerea</i>), <i>Verticillium dahliae</i> (<i>V. dahliae</i>), and <i>Pellicularia sasakii</i> (<i>P. sasakii</i>) were evaluated. Notably, compounds (<i>E</i>)-6-bromo-4-(ethoxyimino)-<i>N</i>-(4-methoxyphenyl)chromane-2-carboxamide and (<i>E</i>)-4-(ethoxyimino)-<i>N</i>-(4-methoxyphenyl)-6-methylchromane-2-carboxamide exhibited remarkable in vitro antibacterial activities against <i>Xoo</i> and <i>Xac</i>, with EC₅₀ values of 30.96 and 56.30 μg/mL, respectively, surpassing those of bismerthiazol. In contrast, the target compounds displayed relatively weaker in vitro antifungal activities against the tested fungi compared to carbendazol and hymexazol. To the best of our knowledge, this represents the first report on the antibacterial and antifungal activities of this series of novel 4-chromanone-derived compounds incorporating carboxamide and oxime ether moieties.</p>