Writing in Contemporary Christian, Country, and Pop styles, his songs have been recorded by Little Big Town, Faith Hill, Garth Brooks, Babyface, Amy Grant, Rich Mullins, Joe Cocker, Kathy Mattea, Martina McBride, Wynonna Judd, Trisha Yearwood, Bonnie Raitt, Susan Ashton, Michael W. Smith, Jill Phillips, Michael Crawford, Peter Frampton, Casting Crowns and Eric Clapton, whose version of Kirkpatrick's "Change the World" won the Grammy Award for Song of the Year.
He co-wrote 12 of the 16 tracks on the Deluxe Edition, including the first song that Little Big Town sang together called "Love Profound".
Kirkpatrick has said that Karen Fairchild, Jimi Westbrook, Kimberly Schlapman and Philip Sweet have made him feel like the fifth member of the band.
Kirkpatrick served as a primary songwriter on that album, along with Gordon Kennedy and Tommy Sims.
In 2018, it was announced that Wayne and his brother Karey were working together on the score for the musical adaptation of Mrs. Doubtfire, based on the film of the same name.
[4] In September 2023, Kirkpatrick and songwriter and musician Don Chaffer were announced to be working on a musical based on the Bluebird Café in Nashville.