[2][3] It is designated as a core route in Canada's National Highway System, comprising a portion of a key international corridor that stretches from Alaska into Mexico.

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.

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.

The former number was transferred to Highway 17 that straddles the Alberta/Saskatchewan provincial boundary north and south of Lloydminster.

The final segment of Highway 43 between Whitecourt and Valleyview was officially completed in 1955 and a ribbon-cutting ceremony was held in the Iosegun River valley, approximately 20 km southeast of Fox Creek.

The completion of the highway provided the south Peace Region of northwest Alberta, particularly Grande Prairie and Valleyview, with a more direct and significantly shorter route to Edmonton.

It also slightly shortened the driving distance from Peace River to Edmonton once the Highway 34 realignment north of Valleyview was completed by 1959.

By 1960, the entire length of the highway was paved, which included a significant realignment between Whitecourt and Cottonwood Corner south of Blue Ridge and other minor realignments between Cottonwood Corner and Gunn to smooth out the highway's numerous jogs.

However, this extension proved to last only until 1998 when the Province completed a second set of highway renumberings in northwest Alberta.

The other segment stretched from west of Highway 733 to Crooked Creek, which included a realignment to bypass Bezanson.

[10] The twinning of two additional segments of Highway 43 was completed in 2007, including 35 km (22 mi) from Asplund Creek (south of Highway 665) to west of Iosegun Lake (south of Little Smoky), and 18.5 km (11.5 mi) from east of Green Court to west of Sangudo.

Highway 43X is the temporary designation of future realignments of Highway 43 in northwest Alberta – one was a partially constructed northwest bypass around Grande Prairie, and the other will act as a south bypass around Whitecourt once constructed in the future.

[2] The first segment of the Grande Prairie bypass, initially signed as Highway 43X, opened to traffic on July 30, 2010 to a twinned standard.

[19] The next segment of the bypass, 10.5 km (6.5 mi) in length, was announced in April 2016[20] and was completed and opened to traffic in September 2019.

[21] The study considers three options, all of which incorporate a direct connection to East Mountain Road.