Abstract: To address the persistent threat of fungal diseases to agricultural production, this study evaluated the antifungal activity of 50 novel cyclopropane oxime ether sulfonamide derivatives. The results of the in vitro antifungal activity assay showed that several compounds exhibited excellent inhibitory effects against Sclerotinia sclerotiorum. Among them, compound 3a-23 displayed the most prominent activity: the inhibition rate was 93.63% at 50 mg/L, which was comparable to those of the control fungicides boscalid (97.35%) and carbendazim (98.41%), with an EC₅₀ value of 0.39 mg/L, which was higher than that of boscalid (0.22 mg/L). The results of in vivo pot experiments demonstrated that compound 3a-23 possessed significant control efficacy against Sclerotinia stem rot of oilseed rape, with a control efficacy of 91.67% at 200 mg/L, lower than that of the control fungicide boscalid (96.67%), and its EC₅₀ value was 36.10 mg/L, higher than that of boscalid (29.96 mg/L). Through conductivity measurement, propidium iodide (PI) staining assay, reactive oxygen species (ROS) detection, and morphological observation, the mechanism of action of compound 3a-23 was preliminarily elucidated: 3a-23 could increase the cell membrane permeability of S. sclerotiorum mycelia, destroy membrane integrity, elevate intracellular ROS levels, cause damage to intracellular ultrastructure, and thereby inhibit mycelial growth. This study provides an important basis for the development of novel fungicides against Sclerotinia sclerotiorum.