Chilli (Capsicum annuum L.) is one of the most important vegetable as well as spice crops grown worldwide for its wide usage. Production of chilli is profoundly affected by anthracnose disease which is one of the most serious and destructive fungal diseases of chilli, especially in tropical and subtropical regions causing around 60–80% yield loss under severe infection. In order to understand the pattern of gene expression and development of molecular markers in chilli for management of anthracnose disease, transcriptome analysis of a resistant (IIVRC-452) and susceptible (Pusa Jwala) genotypes was carried out. Transcriptome data yielded a total of 53,921,012 and 50,079,890 reads with HQ bases 5.18 GB and 4.78 GB of FASTAq sequences and were used for de novo assembly of transcriptome for IIVRC-452 and Pusa Jwala, respectively. More than 50 thousand unigenes were identified in each genotype and around 40,000 of them could be annotated with 30% cut off identity. Digital gene expression analysis revealed a total of 3124 transcripts differentially expressed in resistant and susceptible lines. A total of 871 differential transcripts were annotated and 814 differential genes were present in both resistant and susceptible lines. Furthermore, five key candidate genes (CaLOX, CaLAG-1, CaPG, CaCYP76A2, and CaSAP-13) in pathogen-responsive pathway were identified by quantitative real-time PCR (qRT-PCR). Transcriptome data generated in the present study is a valuable resource for focused investigation on plant–pathogen-interaction, to study the pathways involved in resistance mechanism and to identify markers for use in resistance breeding programmes.