SARS-CoV-2 has mutated rapidly since its first case report in Wuhan, China, leading to the emergence of an indefinite number of variants. India has witnessed three waves of the COVID-19 pandemic. The country saw its first wave of SARS-CoV-2 illness from late January 2020 to February 2021. With a peak surge of cases in mid-September 2020, India recorded more than 11 million cases and a death toll of more than 0.165 million at this time. India faced a brutal second wave driven by the emergence of highly infectious SARS-CoV-2 variants B.1.617.2 (Delta variant) and the third wave with the leading cause of BA.2 (Omicron variant), which has led to an unprecedented rise in COVID-19 cases in the country. On September 14, 2022, India recorded a cumulative 44.51 million cases of COVID-19 with more than 0.528 million deaths. The discovery of common circulating mutants is facilitated by genome sequencing. The changes in the Spike surface glycoprotein recombinant binding domains served as the critical alterations, resulting in enhanced infectivity and transmissibility, with severe clinical effects. Further, the predominant mutation in the SARS-CoV-2 spike protein; the D614G strains served as a model for vaccine development. The mutation of the Wuhan strain to the Variant of Concern led to a significant increase in SARS-CoV-2 infections. In addition, there was a shift in the age group affected by SARS-CoV-2 variant infection. The current review summarized the COVID-19 pandemic's Variant of Concern and the advent of SARS-CoV-2 in India.