Chaetomium globosum is a potential biological control agent effective against various plant pathogens. Several reports are available on the mycoparastism and antibiosis mechanisms of C. globosum against plant pathogenic fungi, whereas a few states induced resistance. The potential induced defense component of C. globosum (Cg-2) was evaluated against early blight disease of tomato (Solanum lycopersicum) and further, global RNA sequencing was performed to gain deep insight into its mechanism. The expression of marker genes of hormone signaling pathways, such as PR1, PiII, PS, PAL, Le4, and GluB were analyzed using real-time quantitative reverse transcription PCR (qRT-PCR) to determine the best time point for RNA sequencing. The transcriptome data revealed that 22,473 differentially expressed genes (DEGs) were expressed in tomato at 12 h post Cg-2 inoculation as compared with control plants and among these 922 DEGs had a fold change of −2 to +2 with p < 0.05. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that most of the DEGs were belonging to metabolic pathways, biosynthesis of secondary metabolites, plant–pathogen interaction, chlorophyll metabolism, and plant hormone signal transduction. Gene Ontology (GO) analysis revealed that DEGs were enriched mainly related to binding activity (GO:0005488), catalytic activity (GO:0003824), metabolic process (GO:0008152), cellular process (GO:0009987), response to stimulus (GO:0050896), biological regulation (GO:0065007), and transcription regulator activity (GO:0140110). The gene modulations in hormone signaling transduction, phenylpropanoid biosynthesis, and mitogen-activated protein kinases (MPK) signaling indicated the upregulation of genes in these pathways. The results revealed active participation of jasmonic acid (JA) and salicylic acid (SA) signaling transduction pathways which further indicated the involvement of induced systemic resistance (ISR) and systemic acquired resistance (SAR) in the systemic resistance induced by Cg-2 in tomato.