Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is readily transmitted from person to person. We evaluated the emerging landscape of SARS-CoV-2 variants in Bangladesh from a retrospective study of nasopharyngeal swabs collected from 130 SARS-CoV-2-positive cases randomly selected over 6 months. Mutation analysis of whole-genome sequencing of 130 SARS-CoV-2 variants revealed 528 unique coding mutations, of which 102 were deletions, 6 were premature stop codons, and the remaining were substitutions. The most common mutation in the cohort was ORF1b:P314L, with a frequency of 98.5%. A total of 132 unique coding mutations were observed in the spike protein gene. Fourteen mutations were mapped to the spike protein receptor binding domain (RBD). These mutations increase the affinity between the spike protein and its human receptor, angiotensin converting enzyme 2 (ACE2), thereby increasing SARS-CoV-2 transmissibility. This study will help understand the SARS-CoV-2 virus and ultimately aid in monitoring and combatting the COVID-19 pandemic by furthering research on appropriate therapies. Analysis of age revealed closer association of the Delta variant with older populations and of the Omicron variant with younger populations. This may have important implications on how we monitor infections, distribute vaccines, and treat patients based on their ages.