The 25-year-old appears topless in the cover, which bills the interview with him to cover "sex, psychedlics and the secrets of stardom".
Styles previously appeared on the cover of Rolling Stone in 2017 when he was 23.
Fans are hoping Styles will also address rumours that he is set to take part in a major new film, after reportedly turning down the role of Prince Eric in Disney's live-action remake of The Little Mermaid.
He is apparently seeking a new project after receiving acclaim for his role in Christopher Nolan's box office hit Dunkirk in 2017.
Earlier this year, the former One Direction star and now-solo artist auditioned for the role of Elvis Presley in Baz Luhrmann's biopic of the rock and roll singer, but lost the part to US actor Austin Butler.
The interview will likely also feature discussion of potential new music, following the release of Styles's self-titled, critically praised debut album in 2017.
The next issue of Rolling Stone is out on 3 September.