We evaluated the in vitro activity of olorofim against Coccidioides species. Olorofim demonstrated potent in vitro activity against all isolates tested with a minimum inhibitory concentration (MIC) range ≤0.008-0.06 µg/mL and geometric mean MIC of 0.010 µg/mL. This activity was also maintained against isolates with elevated fluconazole MICs (≥16 µg/mL), including strains with MICs ≥32 µg/mL (olorofim MIC range ≤0.008-0.06 µg/mL and geometric mean MICs of ≤0.009 and ≤0.013 µg/mL, respectively).