In the 1990s Cochrane took his family to West Africa, where he helped to raise awareness and money for the World Vision famine relief organization. That experience shaped his next album Mad Mad World which contained "Life Is a Highway". Places mentioned in the song are Mozambique, Memphis, Khyber Pass and Vancouver.
The song was Cochrane's only Top 40 hit in the United States.
The plot for the video is a pastiche of the 1991 Canadian dark comedy, Highway 61. The song was originally offered by Capitol Records to the film's director, Bruce McDonald, to use in the film. McDonald declined the offer, citing that the song was "too poppy".
In 2006, American country band Rascal Flatts recorded a cover of this song for the Disney/Pixar animated film Cars. The movie was released on June 9, 2006. The song sold a large quantity of digital downloads, leading to a top ten peak on the Billboard Hot 100. In addition, the cover was placed as a bonus track on later versions of the album Me and My Gang, and also was included on their Greatest Hits Volume 1. This version also won the "Favorite Song from a Movie" award at the 33rd People's Choice Awards. The instrumental of the Rascal Flatts' cover version was prominently featured in the Top Gear American special aired February 11, 2007. The song is included on the soundtrack for Lego Rock Band. It topped the 2 million mark in paid downloads as of the chart dated March 28, 2009. As of March 2013, the song has sold over 3 million copies in the US.
The music video portrays the three band members pulling into a drive-in theater driving three vintage vehicles. The cars allude to three characters from the movie: Lightning McQueen, Doc Hudson and Mater. As the projector rolls, scenes from the Disney/Pixar movie Cars are shown as the band plays through the number. It was directed by Shaun Silva.
The Rascal Flatts version subsequently became a hit on the US Billboard Hot 100 chart, where it peaked at number #7. Even though it was not officially released to country radio, many country stations played the song as an album cut, overlapping with their then-current country single "My Wish". The unsolicited country airplay brought "Life Is a Highway" to number #18 on the US Country Song chart.
In 1998, Chris LeDoux released a cover of "Life Is a Highway" on the album One Road Man. Changes include the timing of vocal entrances on the chorus, and location names between the first and second chorus. The locations in his version are Tennessee, L.A. (Los Angeles), San Antone (San Antonio) and (Las) Vegas. This version reached number No. 64 on the country music chart.