Lumpy Skin Disease Virus (LSDV) is a transboundary pathogen that affects cattle, causing significant economic losses, particularly in Africa and Asia. While the virus was originally endemic to sub-Saharan Africa, it has rapidly spread to Europe, the Middle East, and Asia, necessitating comprehensive genomic surveillance. Despite LSDV’s African origins, genomic data from West and Central Africa remain scarce, limiting insights into regional viral evolution and vaccine compatibility. In this study, molecular detection of LSDV was carried out on cattle samples from Nigeria, Cameroon, and Benin. However, comparative genomic analysis was performed using two near-complete LSDV genomes obtained from Cameroon. Phylogenetic evaluation revealed that LSDV strains from Nigeria and Cameroon cluster within the classical 1.2 lineage. Furthermore, the two sequences from this study cluster with the only publicly available sequence from West and Central Africa, supporting earlier findings of the presence of a West/Central African sub-lineage. Functional genomic analysis identified mutations in genes encoding ankyrin repeat Kelch-like proteins, and envelope proteins involved in immune evasion and viral virulence, raising concerns about vaccine effectiveness. Furthermore, the detection of LSDV in flesh flies (Sarcophaga spp.) underlines their potential role in virus transmission. These findings highlight the importance of genomic monitoring and targeted surveillance.