The road was built in 1887 as an unnamed path linking Nathan Road and Chatham Road, about the site of the former Tsim Sha Tsui Bay. In March 1909, the road was given its current name in honour of Sir Hormusjee Naorojee Mody, a successful Parsi businessman in Hong Kong for his support in founding the Hong Kong University, along his other contributions to Hong Kong.
In the 1970s, Tsim Sha Tsui East was built on reclaimed land over Hung Hom Bay, Mody Road was then extended East to its present-day end at Science Museum Road and since became the principal thoroughfare of Tsim Sha Tsui East. A public square in the area, Mody Square, was named after the road.
A pedestrian tunnel linking Tsim Sha Tsui and East Tsim Sha Tsui MTR station was built under a stretch of Mody Road. The Tsim Sha Tsui East bus terminus is also located along the road, near MTR exit P1.