The 'Disposable Teens' artist revealed that Depp plays drums and lead guitar on the LP's bonus track.
The song is a cover of Carly Simon's 'You're So Vain', which Manson described as "ironic".
"We did a cover version together of a song which we thought was ironic for each other," Manson told MTV News.
"He played drums and lead guitar, and I played guitar and sang. It's a bonus track on my record and the video will probably be us looking at each other like a mirror."
Manson said that the Pirates of the Caribbean star's 9-year-old son also features on the track.
"Johnny's son Jack - whose birthday I'm gonna be performing at - was in the room and he actually played on the song too," he explained. "It's pretty cool."
Manson added of his friendship with Depp: "I met Johnny when I was 19 when I was an extra on 21 Jump Street. I bought his daughter her first pair of high heels when she was wearing diapers, so we've been friends for a long time."
Manson's eighth studio album Born Villain will be released on May 1.
Depp revealed in 2005 that his portrayal of Willy Wonka in Charlie and the Chocolate Factory was based on Manson.
Listen to Marilyn Manson's 'New Reflection' from Born Villain below: