The street begins at New Praya, Kennedy Town (堅彌地城新海旁) at the Victoria Harbour shore of the town, at Belcher Bay, and extends south into Mount Davis. It crosses two of the main streets of Kennedy Town: Catchick Street (吉席街) and Belcher's Street. To the south, Smithfield forms T-intersections with Rock Hill Street (石山街), Forbes Street (科士街), Pokfield Road, Lung Wah Street (龍華街). It ends at a junction with Pok Fu Lam Road and Mount Davis Road (摩星嶺道).
The area bound by the present day Rock Hill Street and Pokfield Path (蒲飛徑) was historically the site of a cattle quarantine depot and a slaughterhouse to house and slaughter live cattle when the animals first arrived in Hong Kong via the piers in Kennedy Town. The Kennedy Town Slaughterhouse was established in 1894.
Smithfield was an area frequented by people who worked as labourers at the cattle station, and the marketplaces nearby that have since become the Forbes Street Temporary Playground (科士街臨時遊樂場) and the North Street (北街) red minibus terminus, and for the loading and unloading of sea cargo coming in and out of the piers of Kennedy Town.
The British novelist Martin Booth wrote in his 2004 autobiographical Gweilo: Memories of a Hong Kong Childhood: "the bellow of a cow in the Kennedy Town abattoir might lift up to me – to be abruptly cut short".
In 1961, the government decided that the slaughterhouse was to be relocated to the Kennedy Town Abattoir at Cadogan Street, and it moved in 1968. Despite calls to convert the original slaughterhouse site into a swimming pool, the government said in 1969 that the plan was not feasible until both the cattle depot and the former slaughterhouse complex (then occupied by the cattle depot as well) were released for redevelopment. The cattle depot was closed down in 1986, when the government finally decided that it was to be removed. The land was subsequently developed into the Kennedy Town Swimming Pool (堅尼地城游泳池, now demolished), Smithfield Market (士美非路街市) and the Smithfield Municipal Services Building.