Maines' first commercially released work was background vocals on Pat Green's debut album, Dancehall Dreamer, produced by her father Lloyd Maines and released in 1995. In late 1995, at the age of 21, Maines joined the all-female country music band Dixie Chicks which has been performing since 1989. Maines replaced founding lead singer Laura Lynch, and also plays a variety of different guitars for the band.

Maines co-wrote four tracks for the Dixie Chicks' first three albums, including the Billboard Hot Country Singles & Tracks Chart number one hit "Without You" on Fly. Maines was a primary songwriter on all 14 tracks of the band's 2006 album Taking the Long Way which peaked on the Billboard Top 200 Chart at number one. Taking the Long Way includes the Hot Country Songs top-40 single "Not Ready to Make Nice," for which the band won the songwriting Grammy award, Song of the Year. Maines considers the songwriting she did for Taking the Long Way "pure therapy" after the controversy that ensued over a comment Maines made from the stage in London that was seen as criticizing U.S. President George W. Bush. "Everything felt more personal this time," Maines said about the album, "...there's just more maturity, depth, intelligence...[These songs] feel more grown-up."

Maines collaborates with other musical artists, both as a Dixie Chick and an individual singer. The Dixie Chicks first worked with rocker Sheryl Crow in 1999 while performing for the concert tour Lilith Fair. Since then, the Dixie Chicks have worked with Crow on her Sheryl Crow and Friends: Live from Central Park album, a Crow remixed version of "Landslide" performed by the Chicks, and the Dixie Chicks song "Favorite Year" from Taking the Long Way. Other artists Maines has worked with include Pat Green, Charlie Robison, Yellowcard, Stevie Nicks, Patty Griffin and Pete Yorn.