The album influences the band's rock sound with that of country music following the success of a country version of the band's 2006 single "Who Says You Can't Go Home", a duet with Jennifer Nettles, which reached No. 1 on the U.S. country chart in May 2006. Following the success had with the duet version of "Who Says You Can't Go Home", there are two songs on the album produced in collaboration with other artists, namely "We Got It Going On" featuring Big & Rich and "Till We Ain't Strangers Anymore" featuring LeAnn Rimes.
After its first week on sale, Lost Highway entered the Dutch, German, Swiss, and Japanese album charts at No. 1, and the UK Album Chart at No. 2, below The Traveling Wilburys Collection. It entered the Irish and Australian charts at No. 5, although after the conclusion of Bon Jovi's Australian tour the album climbed to No. 2. In Japan, the album debuted at No. 1 and sold 73,212 copies in its first week of release on Oricon charts. This is the fourth such time, breaking the Beatles and the Bay City Rollers' record as a Western band (under Oricon's definition) of having three number one albums in the country. In the UK the album sold 79,000 copies in its first week, an improvement on Have a Nice Day's first-week sales of 54,000. In Denmark, the album debuted at No. 5, but went to number one after five weeks on the charts. In the U.S., the album debuted at number one on the Billboard 200 with 292,000 copies sold in its first week. The album was certified platinum by RIAA and as of October 2008, it has sold 1,221,000 copies in the United States and over 4 million copies worldwide.
In the summer of 2007, Bon Jovi performed ten concerts around the world as part of the Lost Highway promotion, with plans for a full greatest hits world tour in 2008. However, after Lost Highway did better than expected, the world tour was moved forward to the fall of 2007, and was renamed the Lost Highway Tour. The tour so far consists of ten dates in New Jersey, followed by Canadian and Japanese tours, as well as the band's first stadium concert in New Zealand since the These days tour. The tour also saw them play Australia for the first time since their brief appearance at the Rumba Festivals in 2002, playing sold out shows in Melbourne, Sydney and Perth. The band then toured the U.S. and Europe in spring and summer 2008, before returning to North America for a few more summer shows, including a free concert in Central Park in New York City.