As the novel coronavirus SARS-CoV-2 continues to spread in all countries, there is a growing interest in monitoring and understanding the impact of emerging strains on virus transmission and disease severity. Here, we analyzed SARS-CoV-2 genomic sequences collected in the Eastern Mediterranean Region (EMR) countries, as of 12 November 2020. The majority (73.7%) of these sequences originated from four out of 22 EMR countries, and 65.6% of all sequences belonged to GISAID clades GR, GH, and G. We identified ten common non-synonymous mutations represented among SARS-CoV-2 in the EMR and several country-specific ones. Two substitutions, S_D614G and NSP12_P323L, were predominant in most countries. Contrary to previous studies, these substitutions were not consistently associated with increased case fatality rates across the Region. Our study identified critical data gaps in EMR highlighting the importance of enhancing surveillance and sequencing capacities in the region.