Objective: Several distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged in different regions worldwide, including Vietnam. This study was conducted is to understand the molecularly genetic epidemiology of SARS-CoV-2 which has not yet been systematically investigated in Vietnamese clinical setting. Subject and method: We analyzed 671 Vietnamese full-length SARS-CoV-2 sequences available on the Global Initiative on Sharing All Influenza Data (GISAID) with data available by 19 October 2021. Sequence variation was done using CoVsurver mutations App (https://www.gisaid.org/epiflu-applications/covsurver-mutations-app/). Phylogenetic tree was built using nextclade algorithms. Result: Our report highlighted that there has been a substantial change in the molecular epidemiology of SARS-CoV-2 circulating through last three waves and ongoing wave of COVID-19. Currently, the Delta variant was dominant with widespread national level. The Alpha variant was almost disappeared and other VOCs, including Beta, Gamma were speculated to be not circulating yet in Vietnam. Conclusion: Surveillance of the emergent variants of SARS-CoV-2 requires an expanded research program to improve our understanding of emerging SARS-CoV-2 mutations profile and their impact on the protective immunity against variants with these mutations. In addition, our surveillance for molecular epidemiology of SARS-CoV-2 in Vietnam will contribute to the efforts at the global levels to fight the pandemic.