The emergence of numerous variants of SARS-CoV-2 has caused massive setbacks and prolonged the COVID-19 pandemic. Some of the variants are still under investigation, while some have become a reason of grave concern. One such variant is B.1.617.2, known as the Delta variant, which was first detected in India. A comprehensive analysis and comparison of this particular variant have been done to the original Wuhan strain, and the possible reasons behind rapid mutation have also been discussed.A comprehensive literature search was done to summarize the information on the variants of SARS-CoV-2 and the reasons behind their mutation, with a significant focus on the B.1.617.2 variant. Data were collected from various online sources such as PubMed, Google Scholar, MEDLINE, Worldometer, WHO, CDC, and GISAID. In addition, 3D structures of spike proteins were obtained from Protein Data Bank (PDB).The data shows that the spike protein of the B.1.617.2 strain is highly mutated and has accumulated eight amino acid changes. Besides spike protein, changes in non-structural proteins (nsP2, nsP3, nsP4, nsP12, and nsP15), other structural proteins (nucleocapsid and membrane protein), and accessory proteins (ns3, ns7a) have been observed as well. Furthermore, in almost all the variants of SARS-CoV-2, D614G mutation occurs, suggesting its role in increased infectivity and transmission.New variants are continuously emerging on which we have no control. Spike mutations are more favored and essential in the evolution of new variants because it increases the transmissibility and infectivity of the virus. Therefore, to maximally protect public health, knowledge of different variants is essential.