Setosphaeria turcica f. sp. sorghi and S. turcica f. sp. zeae, the two formae speciales of S. turcica, cause northern leaf blight disease of sorghum and corn, respectively, and often cause serious economic losses. They show obvious host specialization and have a close evolutionary relationship. Genomic sequencing can provide more information for understanding the virulence mechanisms of pathogens. However, the complete genomic sequence of S. turcica f. sp. sorghi has not yet been reported, and no comparative genomic information is available for the two formae speciales. In this study, based on the analysis of genomic structure, there were more protein-coding genes in S. turcica f. sp. sorghi than S. turcica f. sp. zeae, showing positive selection in the evolution of S. turcica. The results of genomic functional analysis showed that the two formae speciales had a large number of identical protein-coding genes, while there were also specific protein families, including metabolic pathway proteins, transport proteins, CAZys, pathogen and host interaction proteins. We also investigated the expression of specific effector-coding genes in S. turcica f. sp. zeae, and found that the endo-1, 4-β-D-glucanase coding gene CEL2, an important component of cellulase, was significantly up-regulated during the interaction process. Finally, gluconolactone inhibited cellulase activity and decreased infection rate and pathogenicity, which indicates that cellulase is essential for maintaining virulence. These findings demonstrate that cellulase plays an important role in the pathogenicity of S. turcica f. sp. zeae.