The sudden rise in COVID-19 cases in 2020 and the incessant emergence of fast-spreading variants have created an alarming situation worldwide. Besides the continuous advancements in the design and development of vaccines to combat this deadly pandemic, new variants are frequently reported, possessing mutations that rapidly outcompeted an existing population of circulating variants. As concerns grow about the effects of mutations on the efficacy of vaccines, increased transmissibility, immune escape, and diagnostic failures are few other apprehensions liable for more deadly waves of COVID-19. Although the phenomenon of antigenic drift in new variants of SARS-CoV-2 is still not validated, it is conceived that the virus is acquiring new mutations as a fitness advantage for rapid transmission or to overcome immunological resistance of the host cell. Considerable evolution of SARS-CoV-2 has been observed since its first appearance in 2019, and despite the progress in sequencing efforts to characterize the mutations, their impacts in many variants have not been analyzed. The present article provides a substantial review of literature explaining the emerging variants of SARS-CoV-2 circulating globally, key mutations in viral genome, and the possible impacts of these new mutations on prevention and therapeutic strategies currently administered to combat this pandemic. Rising infections, mortalities, and hospitalizations can possibly be tackled through mass vaccination, social distancing, better management of available healthcare infrastructure, and by prioritizing genome sequencing for better serosurveillance studies and community tracking.