The highway, named for the Yellowhead Pass, is a major interprovincial route in Western Canada that runs from Winnipeg to Graham Island off the coast of British Columbia via Saskatoon and Edmonton. It stretches across the four western Canadian provinces of British Columbia, Alberta, Saskatchewan, and Manitoba.

The Yellowhead Highway is part of the Trans-Canada Highway system and the larger National Highway System, but should not be confused with the more southerly, originally-designated Trans-Canada Highway. The highway was officially opened in 1970. Beginning in 1990, the green and white Trans-Canada logo was used to designate the roadway.

The main Yellowhead Highway has been designated as Highway 16 for its entire length since 1977. Prior to this, only the Alberta and British Columbia portions of the highway were designated with this number.

A spur of the Yellowhead Highway, Highway 5, also known as the Southern Yellowhead Highway, connects the main highway at Tête Jaune Cache midway between the Alberta-British Columbia border and Prince George. The highway continues past Kamloops before following the Coquihalla Highway to Hope. Unlike Highway 16, route 5 is not branded as being part of the Trans-Canada system and retains the original Yellowhead signage (whereas Highway 16 uses the Trans-Canada Highway logo).