In his teenage years, Cherone turned to singing in local bands and was heavily influenced by the reigning rock frontmen of the day, most notably Roger Daltrey of The Who, Steven Tyler of Aerosmith, and Queen’s Freddie Mercury. In 1979 Cherone and drummer friend Paul Geary along with guitarist Matt McKay, formed a hard-rock band called Adrenalin, which performed locally. In 1981, they changed the band’s name to The Dream and recorded a six-song independent vinyl EP.

By most band standards the album would be considered an unmitigated commercial success but by Van Halen’s standards it was considered a flop. Neither the album nor the supporting tour performed to financial expectations since Van Halen III was the first album in the band’s career to not achieve at least double platinum status. However, the tour was well received by fans. The tour brought back many older Van Halen songs that fans had wanted to hear since Roth’s initial departure in 1984. This was largely because Hagar refused to play all but the most famous of Roth-era songs. Unlike the band’s subsequent 2004 and 2007–08 tours, Van Halen toured outside of North America in 1998, playing dates in Japan, Europe and for the first time, Australia and New Zealand. One date in Australia was filmed and aired on MTV.

In 1985, Cherone and Geary met guitarist Nuno Bettencourt and bassist Pat Badger in an altercation over a dressing room, but the rivals soon became collaborators and shortly after the combined foursome took the name Extreme, and began writing their own material. The name Extreme came from a play on the words “Ex-Dream”. By the late 1980s, the group had attracted a large regional following; in 1987, the band signed with A&M Records, which released their self-titled debut album in 1989. Selling over 250,000 copies, the band’s debut album justified a second, and in 1990 the band recorded the critically acclaimed Extreme II: Pornograffiti, a mix of hard rock, funk, and pop propelled by Bettencourt’s guitar playing. The album’s lyrical content, mostly written by Cherone, was loosely based on the concept of a fictional young boy named “Francis” and his observations of a decadent, corrupt, and misogynistic society.

Although well received by the rock world in the press, initial sales and chart success for the album were sluggish until A&M released the acoustic ballad “More Than Words” in the early spring of 1991. The song was picked up by mainstream radio and became a huge smash, reaching No. 1 on the Billboard Hot 100 that summer. Extreme II: Pornograffiti was eventually certified double platinum. Also in 1991, Extreme toured in support of David Lee Roth.

Cherone’s career came full circle in April 1992 when he performed “Hammer to Fall” onstage with the three surviving members of Queen at The Freddie Mercury Tribute Concert at Wembley Stadium. Extreme also performed a medley of Queen hits during the first half of the concert. Later that year, Extreme released III Sides To Every Story, a concept album.

Extreme’s 1995 recording, Waiting for the Punchline, was a stripped-down affair that was only modestly successful. After the supporting tour, Bettencourt became dissatisfied and left the group to launch a solo career. Extreme officially folded almost immediately afterward.

In 1996, rock band Van Halen had a falling out with their second lead singer, Sammy Hagar, who had been with the band since 1985. After a failed reunion attempt with original lead vocalist David Lee Roth, who had been with Van Halen from 1974 to 1985, Van Halen was once again without a lead vocalist. At the urging of Van Halen’s manager, Ray Danniels (who also managed Extreme), Cherone was called for an audition. Guitarist Eddie Van Halen liked Cherone’s lyrics, as well as his work ethic, and in November 1996 Cherone became Van Halen’s third lead vocalist. That year, Cherone took up residence in Eddie’s guest house and spent the next year writing and recording a new studio album.

Released on March 17, 1998, Van Halen III debuted at No. 4 on the Billboard 200 album chart, selling 197,000 copies in its first week then 500,000 by summer (RIAA gold certified in the United States) and over 700,000 copies as of 2011. The album featured an eclectic and diverse set of songs, marking a departure from the straightforward arena rock that Van Halen had played with Hagar and contrasting with the tongue-in-cheek bombast that originally attracted Van Halen fans to Roth. Van Halen III’s songs were often longer and more lyrically intricate than earlier Van Halen material, giving it a progressive influence. The album only produced a sole No. 1 Billboard Mainstream Rock hit in “Without You”.

In February 2003, just one week after The Station nightclub fire, Gary and his brother Markus performed “More Than Words” during a memorial service for the victims. The memorial was broadcast live on WHJY in Providence, RI.

Since 2004 Extreme have re-united with Cherone on several occasions for “one off” shows in their home town and in New England, but in November 2007 they announced plans to do another world tour along with a new album.

In 2005, Cherone released a four-song sampler CD, Need I Say More, that was written and produced by Steve Catizone and Leo Mellace. This album was recorded by Jeff Yurek at Sanctum Sound in Boston, Massachusetts, and mixed by Carl Nappa in New York City. Musicians including Dave DiCenso (drums), Baron Browne (bass) and Steve Hunt (keyboards) are also featured on the record.

In May 2006, Cherone sang in three shows as part of Amazing Journey, a tribute to The Who created by ex-Dream Theater drummer Mike Portnoy, featuring Paul Gilbert on guitar and Billy Sheehan on bass. Not long after, Gary and his brother Markus Cherone created their own tribute to The Who, Slip Kid. Presently the band continues to perform regularly in the Greater Boston area.

The album Saudades de Rock was released in August 2008.

Cherone has formed a new band with his brother Markus on guitar, Joe Pessia on bass/mandolin and Dana Spellman on drums. They have released a self-titled debut album in early 2011 and have toured to promote it.

Their follow-up album, “Retro Grenade”, was released in 2014.

In 2016, the band released Pornograffitti Live 25: Metal Meltdown, an audio/video presentation of its 2015 concert at Las Vegas’ Hard Rock Casino.