Leprosy is a chronic infectious disease caused by _Mycobacterium leprae_ that affects almost 500,000 people worldwide^1^. The timing of first infection, geographic origin, and pattern of transmission of the disease are unknown^1-3^. Comparative genomics research has recently suggested _M. leprae_ evolved in East Africa or South Asia before spreading to Europe and the rest of the World^4-5^. The earliest accepted textual evidence indicates that leprosy existed in India by at least 600 B.C. and was known in Europe by 400 B.C.^6-7^. The earliest skeletal evidence was dated 300-200 B.C. in Egypt^8^ and Thailand^9^. Here, we report the presence of lepromatous leprosy in skeletal remains from Balathal, a Chalcolithic site (2300-1550 B.C.) in India^10-11^. A middle aged adult male skeleton demonstrates manifestations of facies leprosa and rhinomaxillary syndrome, degenerative joint disease, infectious involvement of the tibia (periostitis), and injury to the peripheral skeleton, often the result of skin anaesthesia. Paleopathological analysis indicates that lepromatous leprosy was present in India by 1800 B.C., a result which supports some translations of the Atharva Veda that reference leprosy and its treatment in hymns composed before the first millennium B.C.^12^. The presence of leprosy in Chalcolithic India suggests _M. leprae_ may have been transmitted during the second or third millennium B.C., at a time when there was substantial interaction between South Asia, West Asia, and Northeastern Africa^13^. This evidence should be impetus to look for additional skeletal and molecular evidence of leprosy in human remains from this time period in India and Africa to confirm the origin of the disease