In an effort to understand how fungi degrade biomass, we grew Phanerochaete chrysosporium on sorghum stover and chronicled the growth of the fungus over the course of 14 days. The fungal mass grew steadily until the fifth day, reaching 0.06 mg of cells per milligram of dry mass, which fell by the seventh day and stayed at nearly the same level until day 14. After 1 day, hemicellulases, cellulases, and polygalacturonases were detected in the extracellular fluid at 1.06, 0.34, and 0.20 U/ml, respectively. Proteomic studies performed with the extracellular fluid using liquid chromatography–tandem mass spectrometry identified 57, 116, and 102 degradative enzymes targeting cellulose, hemicellulose, pectin, lignin, proteins, and lipids on days 1, 7, and 14, respectively. Significant concentrations of breakdown products of the sorghum polysaccharides were detected in the extracellular fluid indicating that the enzymes were breaking the polysaccharides, and after 14 days, almost 39% of the sorghum sugars had been used by the fungus. Our results suggest that P. chrysosporium produces a set of enzymes to degrade the components of lignocellulose from the beginning of its growth, but modifies the complement of enzymes it secretes over time to adapt to the particular substrate available.