Canine parvovirus (CPV) infection causes severe gastroenteritis in canines with high mortality in puppies. This virus evolved from FPV by altering its transferrin receptor (TfR) followed by emergence of CPV-2 variants in subsequent years by altering the immunodominant VP2 amino acid residues. Though the previous studies analysed VP2 gene, there are limited studies on non-structural protein (NS1 & NS2) genes. In this study, comparative whole genomic analysis was performed with the CPV suspected clinical samples collected Pan-India in 2023 with the repository CPV strains (2009–2019 isolates) and the current Indian CPV vaccine strain. The present pan-Indian study showed that the CPV-2c (N426E) had almost completely replaced the previously dominant CPV-2a variant (N426) in India. The Q370R mutation of VP2 was the most common change in the recent CPV-2c strain (CPV-2c 370Arg variant). Phylogeny showed the existence of three clades among the recent CPV-2c strains. The study identified several new positive selection sites in VP1 (N terminus), VP2, NS1 and NS2 genes in the recent CPV strains indicating emergence of new CPV-2c variants with varied antigenic and replication properties. The predominant ‘CPV-2c 370Arg variants’ were grouped along with the Chinese and Nigerian CPV-2c strains away from the CPV vaccine strain and repositories. VP2 epitope analysis predicted nine amino acid variations (includes 2 new variations) at four potential linear B-cell epitopes in the ‘CPV-2c 370Arg variants’ underlying chance of vaccine failure. This pan-Indian study, laid the foundation for further research concerning the dynamics of virus evolution and understanding genetic mutations.