The history of Highway 43 dates back to the late 1920s or early 1930s. It was originally numbered Highway 17 and, by 1932, it spanned approximately 17 km from Highway 16 to Onoway. By 1938, Highway 17 (now 43) had been extended to Sangudo and it had reached Whitecourt via a jagged alignment with numerous 90° jogs by 1940. Sometime between 1942 and 1946, the highway was renumbered to Highway 43. The former number was transferred to Highway 17 that straddles the Alberta/Saskatchewan provincial boundary north and south of Lloydminster.