This study was endeavoured to contribute in furthering our understanding of the molecular epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by sequencing and analysing the first full-length genome sequences obtained from 48 coronavirus disease-2019 (COVID-19) patients in five districts in Western Serbia in the period April 2020–July 2020. SARS-CoV-2 sequences in Western Serbia distinguished from the Wuhan sequence in 128 SNPs in total. The phylogenetic structure of local SARS-CoV-2 isolates suggested the existence of at least four distinct groups of SARS-CoV-2 strains in Western Serbia. The first group is the most similar to the strain from Italy. These isolates included two 20A sequences and 15−30 20B sequences that displayed a newly occurring set of four conjoined mutations. The second group is the most similar to the strain from France, carrying two mutations and belonged to 20A clade. The third group is the most similar to the strain from Switzerland carrying four co-occurring mutations and belonging to 20B clade. The fourth group is the most similar to another strain from France, displaying one mutation that gave rise to a single local isolate that belonged to 20A clade.