Foot-and-mouth disease (FMD) is posing serious economic losses if not stringently controlled. This study aimed to characterize FMD virus (FMDV) in suspected samples which were collected from cattle and buffalo in Egypt between 2018 and 2020. Pan-serotype FMDV real time reverse transcription PCR (RT-PCR) assay that targets 3D genes of the FMDV were used to the preliminary laboratory diagnosis. The study was also performed with virus isolation on BHK-21 cells, conventional RT-PCR, and sequencing. FMDV serotypes A, O, and SAT2 were detected in all the examined 44 samples. Phylogenetic analysis of VP1 sequence products showed that recent FMDV outbreaks that occurred during 2018, 2019, and 2020 in Egypt were caused by serotypes SAT2 of Lib-12 lineage. Serotype O of East Africa 3 (EA-3) was detected in 2019 samples while serotype A of African topotype/G-IV was detected in 2020. The study findings recommended the significance of booster sampling of representative FMDV from the bordering countries as such protocol might be impacted on FMD control strategy as a transboundary viral disease.