The ascomycete Trichoderma reesei is known as one of the most prolific producers of plant biomass-degrading enzymes. While several mutant strains have been developed by mutagenesis to improve enzyme productivity for a variety of industrial applications, little is known about the mechanical basis of these improvements. A genomic sequence comparison of mutant and wild-type strains was undertaken to provide new insights in this regard. We identified a number of single-nucleotide polymorphisms (SNPs) after sequencing the genome of a hyper-cellulolytic T. reesei strain, PC-3-7, with a next-generation sequencer. Of these, the SNP detected in cre1, the carbon catabolite repressor gene, was found to be responsible for increased cellulase production. Further comparative genomic analysis enabled the identification of an SNP that correlated well with high cellulase production in a T. reesei mutant. These results provide a better understanding of the genetic changes induced by classical mutagenesis and how they correlate with desirable phenotypes in filamentous fungi.