Highway 43 was originally numbered Highway 17, a short gravel road that ran only from Highway 16 to Onoway. It was later extended to Whitecourt and renumbered as Highway 43 in the 1940s, and an extension to Valleyview had been completed by the mid-1950s. In 1991 the highway was extended to included a portion of the existing Highway 34 from Valleyview to Donnelly, but was revised in 1998 to turn west through Grande Prairie, forming a contiguous route from Manly Corner to the border. Due to increasing traffic levels and the province's greater plan to upgrade their portion of the CANAMEX Corridor, work began in the 2000s to twin the entire length of the highway. The Edmonton–Grande Prairie section was completed in summer 2014, and construction began in 2016 on an expressway bypass to the northwest of Grande Prairie. Planning is underway for the remaining section between the BC border and Beaverlodge.