Foot and mouth disease is highly contagious viral disease of swine caused by aphtho virus of family picornaviridae characterised by fever and formation of vesicles on the buccal mucosa, feet and teat. This disease is rarely fatal and have very high morbidity and low mortality. It causes sudden death in young piglets. A study was undertaken regarding the sero-prevalence, hemato-biochemical, clinical signs and histopathological study of FMD in pigs in Western Uttar Pradesh. The present study was undertaken in various places of western Uttar Pradesh for the period of twelve months i.e., from May 2020 to April 2021. A total of 2640 animals from different farms in various places of western UP were selected for the study. The seroprevalence of FMD by enzyme-linked immunosorbent assay (ELISA) was observed as 26.51%. Haematology revealed a decrease in total erythrocyte count (TEC), total leukocyte count (TLC), packed cell volume (PCV) and hemoglobin (Hb) value in the animals found seropositive for FMD in comparison to the seronegative animals. Serum biochemical test results showed an increase in ALT, AST values as well as serum creatinine and BUN values in the animals found seropositive for FMD. Clinical signs includes fever, lameness, blisters and ulcers were seen on the oral mucosa, feet and teats. Gross observation revealed vesicular lesions and ulcerations of the dorsal surface of tongue, snout and foot region, myocarditis and petechial haemorrhage in heart. Microscopically intercellular oedema in the stratum spinosum, micro vesicle formations in skin, inter-alveolar septal thickening due to mononuclear cells infiltration and emphysema in lungs were observed indicating the secondary bacterial infection.