Mulberry is an important crop plant for the sericulture industry. Here, we report high-quality genome sequence of a cultivated Indian mulberry (Morus indica cv K2) obtained by combining data from four different technologies, including Illumina, single-molecule real-time sequencing, chromosome conformation capture and optical mapping, with a gene completeness of 96.5%. Based on the genome sequence, we identified 49.2% of repetitive DNA and 27,435 high-confidence protein-coding genes with >90% of them supported by transcript evidence. A comparative analysis with other plant genomes identified 4.8% of species-specific genes in the M. indica genome. Transcriptome profiling revealed tissue-specific and differential expression across multiple accessions of ~4.7% and 2–5% of protein-coding genes, respectively, implicated in diverse biological processes. Whole genome resequencing of 21 accessions/species revealed ~2.5 million single nucleotide polymorphisms and ~ 0.2 million insertions/deletions. These data and results provide a comprehensive resource to accelerate the genomics research in mulberry for its improvement. •We report a high-quality draft genome sequence of Indian mulberry (M. indica) cultivar K2 containing 49.2% repeat content.•We identified a total of 27,435 high-confidence protein-coding genes with >90% of them supported by transcript evidence.•A comparative analysis with other plant genomes and transcriptome profiling identified species- and tissue-specific genes.•The resequencing of 21 accessions/species revealed ~2.5 million SNPs and ~0.2 million InDels for translational genomics.