Fusarium head blight (FHB), caused by Fusarium graminearum, is a devastating disease that severely affects crop yield and quality worldwide. The catabolite responsive elements A (CreA) plays a critical role in numerous cellular processes in eukaryotes. In this study, we performed a functional characterization of CreA in F. graminearum. Deletion of FgCreA led to the transcriptional upregulation of FgCyp51A and FgErg6A, consequently resulting in elevated levels of ergosterol. This augmented ergosterol content was observed to improve cellular membrane integrity and diminished sensitivity to demethylation inhibitors (DMI) fungicides in F. graminearum. FgCreA is an essential element in carbon catabolite repression (CCR), consequently, the ΔFgcreA mutant was compromised in radial growth on various carbon sources, sexual/asexual development, and deoxynivalenol toxin biosynthesis, which was suppressed due to transcriptional downregulation of the biosynthesis-required enzymes. These results unveil a novel regulatory mechanism of FgCreA, influencing both the pathogenicity of F. graminearum and its sensitivity to DMI fungicides.