The complete sequence for viral protein 2 (VP2) of canine parvovirus (CPV) was obtained from 33 isolates collected from dogs with clinical symptoms and a vaccine in Vietnam from Mar 2017– June 2019. Molecular analysis revealed the descent evolution in CPV-2c-“new”, forming a “new var.” sub-lineage of the substantial 5G, 447M mutations restricted to the Vietnamese isolates in the epitope stretches. These were found besides the common 80R, 87L, 93N, 101T, 103A, 232I, 267Y, 297A, 300G, 305Y, 323N, 324I, 334A, 341P, 370R, 426E, 440T, 447I, 555V, 564S, and 568G typical to the “new” CPV-2c. The novel 447M mutation seemed to emerge in recent years in Vietnam and was present in 38 of 58 CPV-2c strains isolated from December 2016 to June 2019 by our retrospective analysis, counting for 65.5%. With strong nodal support (98%), the topology of the phylogenetic tree revealed the substantially distinct Vietnamese sub-lineage of 2c-“new-var.” (5G/426E/447M) separated from the Vietnamese 2c-“new” (5G/426E/447I), within the 2c-(Asia)/Asia-2c. The Asia-2c strains of Vietnam were grouped with the recent Thai, Chinese, Mongolian, Taiwanese, Korean, and the Asian variants newly imported into Italy, Egypt, and Nigeria from Asia. The changes of amino acids in the epitope stretch in VP2 have effective alteration not only on the continual formation of substantial sub- or new genotypic variants but may be of subjects for antigenicity/immunogenicity and virulence to the CPV-2 strains and vaccine failure worldwide.