Foot-and-mouth disease (FMD) is an acute viral animal disease; that causes huge economic consequences to the livestock sector. Totally, 118 samples (Epithelial Tissue (n = 38), Vesicles (n = 30), Heart (n = 31), Tongue (n = 9), Oral swabs (n = 10), and 232 samples (Epithelial Tissue (n = 108), Vesicular fluids (n = 36), Heart (n = 28), Tongue (n = 24), Oral swabs (n = 36) collected from suspected animals during FMD outbreak investigations in 2021, and 2022, respectively, constituted the material of the study. This study aimed to detect the Foot-and-mouth disease viruses (FMDVs) and their serotype using qRT-PCR, and antigen detection using ELISA, followed by virus isolation on BHK-21 cells then identification. The field samples were analyzed by FMDV screening primers/probes then the virus serotype-specific primers/probes revealing 57/118 (48.30%) during 2021, and 158/232 (68.10%) during 2022 positive samples with qRT-PCR and categorized into serotype O 46/57(80.70%), 90/158(56.96%) with the highest prevalence, followed by serotype A 7/57(12.28%), 58/158(36.70%), serotype SAT-2 4/57(7%), 10/158(6.32%) during 2021, and 2022, respectively. FMD antigen detection ELISA was performed giving results with 45/118(38.14%) in 2021, and 120/232(51.72%) in 2022. The virus is propagated successfully in 4/10 (40%) in 2021, and 6/17(35.29%) in 2022 samples. Results illustrated in the present study help in general detection of FMDV serotypes currently circulating in Egypt, and aid in understanding of current status of epidemiological aspect of the disease to construct efficient control plan.