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<i>Candida glabrata</i> has emerged as a leading cause of fungal infections worldwide, characterized by inherent antifungal resistance. While considerable attention has focused on conventional resistance mechanisms, the contribution of epigenetic regulation to <i>C. glabrata</i> pathogenicity remains incompletely understood. Here, we investigated the role of Ubp10, a histone H2B deubiquitinase, in <i>C. glabrata</i> stress adaptation and virulence. Deletion of <i>UBP10</i> resulted in a substantial increase in H2B ubiquitination compared to the wild-type, indicating its predominant role in H2B deubiquitination. Phenotypic characterization revealed that <i>ubp10</i> mutant exhibited impaired growth kinetics, mitochondrial dysfunction with elevated reactive oxygen species production, and altered morphogenetic responses including enhanced agar invasion but reduced biofilm formation. Most notably, the <i>ubp10</i> mutant displayed a distinctive antifungal susceptibility profile with increased resistance to azoles coupled with enhanced susceptibility to echinocandins, correlating with dysregulated expression of drug-response genes (<i>ERG6</i>, <i>ERG11</i>, <i>CDR1</i>, <i>FKS1</i>, and <i>FKS2</i>). Transcriptional analysis further demonstrated that key oxidative stress response genes (<i>CTA1</i>, <i>SOD1</i>, <i>GPX2</i>) were downregulated under basal conditions but hyperactivated upon H₂O₂ exposure. In a murine model of systemic candidiasis, the <i>ubp10</i> mutant was avirulent, with 100% host survival. These findings establish Ubp10 as a multifaceted epigenetic regulator that orchestrates <i>C. glabrata</i> pathobiology through coordinated control of stress adaptation, drug resistance, and virulence mechanisms, potentially offering new targets for therapeutic intervention against this clinically significant pathogen.