Phytopathogenic fungi can weaken the effectiveness of antifungal chemicals from plants and artificial synthesis through a xenobiotic detoxification system.  Nevertheless, the transcription factors responsible for transcriptional activation of xenobiotic detoxification genes in phytopathogenic fungi are rarely reported.  Here, we show that a GATA transcription factor, SsGATA1, regulates the transcription of drug efflux pump genes, thus contributing to tolerance to various types of chemical fungicides, including propiconazole, caspofungin, and azoxystrobin in Sclerotinia sclerotiorum.  Similarly, SsGATA1 also confers tolerance to isothiocyanate and flavonols, two compounds reported as broad-spectrum antifungal chemicals, by mediating the transcription of the isothiocyanate hydrolase SsSaxA.  Importantly, SsGATA1 positively regulates pathogenicity, which is attributed to the upregulation of hydrolases and SsSaxA during infection.  Furthermore, SsGATA1 is responsible for tolerance to several stresses.  Our findings demonstrate that SsGATA1 plays roles in multidrug resistance and pathogenicity by activating the transcription of hydrolases and xenobiotic detoxification genes.