Biological delignification using white-rot fungi is a possible approach in the pretreatment of lignocellulosic biomass. Despite the considerable promise of this low-input, environmentally-friendly pretreatment strategy, its large-scale application is still limited. Therefore, understanding the best combination of factors which affect biological pretreatment and its impact on enzymatic hydrolysis is essential for its commercialization. The present study was conducted to evaluate the impact of fungal pretreatment on the enzymatic digestibility of switchgrass under solid-state fermentation (SSF) using Phanerochaete chrysosporium (PC), Trametes versicolor 52J (Tv 52J), and a mutant strain of Trametes versicolor that is cellobiose dehydrogenase-deficient (Tv m4D). Response surface methodology and analysis of variance (ANOVA) were employed to ascertain the optimum pretreatment conditions and the effects of pretreatment factors on delignification, cellulose loss, and total available carbohydrate (TAC). Pretreatment with Tv m4D gave the highest TAC (73.4%), while the highest delignification (23.6%) was observed in the PC-treated sample. Fermentation temperature significantly affected the response variables for the wild-type fungal strains, while fermentation time was the main significant factor for Tv m4D. The result of enzymatic hydrolysis with fungus-treated switchgrass at optimum pretreatment conditions showed that pretreatment with the white-rot fungi enhanced enzymatic digestibility with wild-type T. versicolor (52J)-treated switchgrass, yielding approximately 64.9% and 74% more total reducing sugar before and after densification, respectively, than the untreated switchgrass sample. Pretreatment using PC and Tv 52J at low severity positively contributed to enzymatic digestibility but resulted in switchgrass pellets with low unit density and tensile strength compared to the pellets from the untreated switchgrass.