The fungal pathogen Colletotrichum falcatum causes the stalks, the economically important for sugar extraction. Although, disease management is achieved by cultivating resistant cultivars, the complex polyploidy of sugarcane genome complicates understanding the inheritance of disease resistance. Earlier attempts of using resistant and susceptible varieties to understand host-pathogen interaction resulted in cultivar specific expression of genes due to different genomic background of the varieties. To avoid host background variation in the interaction, suppression subtractive hybridization (SSH) based next generation sequencing technology was utilized in the same cv Co 7805 which behaves differently as incompatible and compatible to two different C. falcatum pathotypes. In the incompatible interaction (ICI) with C. falcatum pathotype Cf87012 (Less virulent, LVir) 10,038 contigs were assembled from ~54,699,263 raw reads. In the compatible interaction (CI) to the C. falcatum pathotype Cf94012 (Virulent, Vir) 4022 contigs were assembled from ~52,509,239 raw reads. The transcripts homologous to CEBiP receptor and transcripts involved in the signals ROS, Ca2+, BR, JA and ABA were exhibited in both the responses. Additionally, MAPK, ET, PI signals and JA amino conjugation related transcripts were found only in ICI. Finally, the temporal gene expression of a total number of 16 transcripts was monitored in qRT-PCR. Most of the transcripts exhibited highest induction in ICI in comparison with CI. Further, more than 17 transcripts specific to the pathogen were found only in CI, indicating that the pathogen colonizes the host tissue whereas it failed to to do so in ICI. Overall, this study has identified for the first time, the differential responses of a single sugarcane host to two different C. falcatum pathotypes and PAMP triggered immunity (PTI) is exhibited in both the responses, but the more efficient effector triggered immunity (ETI) was found only in ICI at the molecular level.