This study investigates the mechanisms of antifungal resistance in a clinical isolate of *Candida parapsilosis* that is resistant to azoles and echinocandins. The resistant isolate was found to have differential expression of several genes involved in ergosterol biosynthesis, including upregulation of ERG2, ERG5, ERG6, ERG11, ERG24, ERG25, and UPC2. Whole-genome sequencing revealed a mutation in the *ERG3* gene, resulting in a G111R amino acid substitution, which reduced sterol desaturase activity. This mutation was shown to be responsible for the altered susceptibility to both azoles and echinocandins. The study also found that disruption of *ERG3* in both the susceptible and resistant isolates led to high-level azole resistance and an intermediate to resistant phenotype for echinocandins. The G111R substitution in *Erg3* was shown to be the first reported mechanism of ERG3-related resistance in *C. parapsilosis* and the first evidence of such mutations influencing susceptibility to echinocandins in any Candida species.This study investigates the mechanisms of antifungal resistance in a clinical isolate of *Candida parapsilosis* that is resistant to azoles and echinocandins. The resistant isolate was found to have differential expression of several genes involved in ergosterol biosynthesis, including upregulation of ERG2, ERG5, ERG6, ERG11, ERG24, ERG25, and UPC2. Whole-genome sequencing revealed a mutation in the *ERG3* gene, resulting in a G111R amino acid substitution, which reduced sterol desaturase activity. This mutation was shown to be responsible for the altered susceptibility to both azoles and echinocandins. The study also found that disruption of *ERG3* in both the susceptible and resistant isolates led to high-level azole resistance and an intermediate to resistant phenotype for echinocandins. The G111R substitution in *Erg3* was shown to be the first reported mechanism of ERG3-related resistance in *C. parapsilosis* and the first evidence of such mutations influencing susceptibility to echinocandins in any Candida species.