The Duxton Hill area sits on the former 13-hectares nutmeg plantation with 1,800 trees of Dr J. William Montgomerie (1797–1856), who first arrived in Singapore in 1819 and became an Assistant Surgeon in the service of the British colonial government.

Fourteen acres also went to Arab Syed Abdullah bin Omar Aljunied, who divided them into four lots which were leased to wealthy Chinese developers.

Opium and gambling dens, as well as cheap brothels, used to flourish on Duxton Road, and one writer describes it as a slum area and a notoriously vice-ridden environment.

Despite the notoriety of the street, many wealthy Straits Chinese families built and occupied lofty and exquisitely designed residences and shophouses on Duxton Hill.

Buildings in the vicinity of Duxton Hill include the Craig Place, Chinatown Plaza and Apartments and the Singapore Institute of Architects.

By the 2000s, many of the shophouses had been converted to restaurants, bars and cafes popular with local residents and expatriates due to the neighborhood’s close proximity to the Central Business District and downtown.