The plant pathogenic fungus Sclerotinia sclerotiorum is the causative agent of Sclerotinia stem rot (SSR) disease in most dicotyledons. Among the various proteins involved in drug efflux or substance transport, ATP-binding cassette (ABC) transporters constitute a superfamily of membrane-bound proteins that may play a crucial role in the survival of S. sclerotiorum. However, the expression patterns and functions of ABC transporter genes in S. sclerotiorum remain largely uncharacterized. This study characterized a highly expressed S. sclerotiorum ABC transporter gene during inoculation on host plants, SsBMR1. Silencing SsBMR1 resulted in a significant reduction in hyphal growth, infection cushion development, sclerotia formation, and virulence. Moreover, host-induced gene silencing (HIGS) of SsBMR1 significantly enhanced plant resistance. Transcriptome and metabolomics analyses suggested that SsBMR1 is involved in antioxidant and toxin transport, thereby influencing fungal defense and cell rescue mechanisms. In comparison to the wild-type strain, SsBMR1 gene-silenced transformants exhibited a diminished response to extracellar oxidative stress and a decreased exporting of antioxidant glutathione. Tolerance assays further demonstrated the crucial role of SsBMR1 in conferring resistance to the plant antifungal substances, camalexin and brassinin, as well as certain fungicides. Furthermore, SsBMR1 gene-silenced transformants showed enhanced repression on virulence when sprayed with camalexin and brassinin on the leaves. Thus, SsBMR1 likely contributes to virulence by facilitating the export of antioxidant and providing resistance against antifungal agents. The findings of this study provide valuable insights that could contribute to the development of novel management techniques for SSR.