BACKGROUND: Canine parvovirus type-2 (CPV-2) is a highly contagious enteric pathogen of puppies with worldwide distribution. AIMS: Molecular epidemiology, genetic characterization, phylogenetic analysis, and isolation of the CPV-2 virus from clinically affected dogs in Mizoram, India over eight years. METHODS: A total of 202 samples (199 fecal samples, 2 vomita, and 1 tissue sample) were screened by PCR assay. RESULTS: 103 out of 202 samples (50.99%) tested positive. Of the 103 positive samples, 83 samples were cloned and sequenced. Sequence analysis showed CPV-2c as the predominant variant (63.85%) followed by the 2a variant (26.5%), 2b (8.43%), and FPV (1.2%). Phylogenetic analyses of the CPV-2c sequences formed separate clusters and were ancestrally related to Japanese, Chinese, and Italian 2c sequences. Similarly, 2a isolates formed separate clusters under different clades and were ancestrally related to Indian, Singaporean, Japanese, Uruguayan, and Chinese 2a isolates. 2b isolates formed a single cluster with the Chinese 2b isolate. FPV isolate clustered with North American FPV. Both synonymous and non-synonymous mutations (unique to this study) were evident in all the types of CPV-2s indicative of active evolution with regional variation. In the cell culture medium, CPV-2 showed cytopathogenic effects at the third passage level. CONCLUSION: The study, the first in-depth report on CPV-2, showed a shift towards CPV-2c as the predominant variant in Mizoram. This variant clustered separately from current vaccine strains, highlighting the need for extensive epidemiological surveillance to better understand viral phylogenomics and evaluate current vaccine efficacy.