The road is named after William Caine,[1] a Colonial Secretary, and an acting Governor of Hong Kong between May and September 1859.

From 1862–1865 during the American Civil War, Caine Road was home to Sara Delano, the mother of United States President Franklin D. Roosevelt, whose family had a permanent residence at Rose Hill on Caine Road (currently standing near the Immaculate Conception Cathedral of Hong Kong) through their connection to the American trading house Russell & Company.

[2] In the afternoon of 15 December 1941, during the Battle of Hong Kong, a stick Japanese bombs hit the junction of Old Bailey Street and Caine Road, the junction of Pottinger Street and Hollywood Road, Wellington Street and the Central Police Station.

[3] The bombing was part of a systematic bombardment of the Hong Kong Island's north shore that was launched on that day.

Private vehicles may drive west between 7pm and 7am weekdays, after 1pm on Saturdays, and all day on Sundays.