For their sophomore effort, 1984's The Last in Line, the band expanded its lineup to include keyboardist Claude Schnell, as the album would become the biggest hit of Dio's career (on the strength of another MTV-approved video, for the album's anthemic title track) and the group became an arena headliner. Although Dio's next release, 1985's Sacred Heart, was commercially successful, Campbell had become disillusioned by the group's direction and split from the group a year later. Just prior to Campbell's exit, the entire Dio band helped organize Hear n' Aid, an all-star assembly of heavy metal artists that recorded a track called "Stars," which helped fight world hunger (a subsequent album was issued as well, collecting previously unreleased live tracks from a few of the day's top hard rock acts). Former Giuffria guitarist Craig Goldy took Campbell's place, resulting in such releases as 1986's live EP Intermission and 1987's Dream Evil, which retained the group's headbanging audience, but failed to expand upon it as its previous releases had.

By 1990's Lock Up the Wolves, Ronnie James Dio was the only original member of Dio left in attendance as the band's lineup continued to fluctuate throughout the '90s on such releases as 1994's Strange Highways, 1996's Angry Machines, and 1998's Inferno: Last in Live (Ronnie James took a brief break from Dio in 1992 to rejoin Black Sabbath for a lone release, Dehumanizer). In 2000, a pair of Dio releases emerged; first was Dio's first new studio album in four years, the concept album Magica (which saw past members Bain and Goldy return to the group), as well as a 16-track compilation titled The Very Beast of Dio. His medieval-themed metal returned two years later, when the Killing the Dragon album arrived in the spring of 2002. The album was a serious endeavor, but Dio also learned to make fun of his image after years of defending it, inviting comedy duo Tenacious D to star in the video for "Push" and even including the clip on the fall re-release of Killing the Dragon.

In the mid-2000s Dio the man and the band returned with the studio album Master of the Moon and the live Evil or Divine, but by 2006 the band had been sidelined upon the announcement that Ronnie James would be joining Heaven & Hell, a group reuniting the singer with his late-era Sabbath brethren Tony Iommi, Geezer Butler, and Vinny Appice and named after the first Sabbath recording (released in 1980) that featured him as frontman. Heaven & Hell toured in the late 2000s and released a live (Live from Radio City Music Hall) and a studio (Devil You Know) recording, but by November of 2009 it was announced that the singer was suffering from stomach cancer, and Heaven & Hell subsequently canceled their summer 2010 touring plans. Ronnie James Dio succumbed to the disease on May 16, 2010, in Houston, TX.