Species of Sanghuangporus produce abundant bioactive compounds, including flavonoids, polysaccharides, and triterpenoids, among which flavonoids exhibit prominent antioxidant activity and great development potential. Taking the peak extracellular flavonoid (EF) concentration in fermentation broth as the index, we optimized the liquid fermentation media and conditions for three Sanghuangporus strains (wild S. vaninii Z-0090, cultivar S. vaninii Z-0119, and cultivar S. baumii Z-0118) via single-factor experiments and the Box–Behnken response surface methodology. We further evaluated the antioxidant activity of the fermentation broth and analyzed its correlation with EF concentration using Pearson correlation analysis. After optimization, the EF concentrations of strains Z-0090, Z-0119 and Z-0118 were increased by 22.82%, 13.47% and 16.66%, respectively, compared with the control group. Antioxidant assays showed that strain Z-0090 had the highest hydroxyl radical scavenging rate (88.63%), strain Z-0119 presented balanced performance across all antioxidant indicators, and strain Z-0118 exhibited the strongest ABTS radical scavenging capacity (184.96 μg Trolox equivalents/mL), which was highly correlated with its EF concentration. This study provides a theoretical basis for the application of Sanghuangporus EFs in food, medicine, and industrial flavonoid production.