Gossard and Ament were floored with the results, immediately inviting Vedder up to Seattle, where he soon landed the gig. Shortly after lead guitarist Mike McCready joined the band (plus a revolving door of assorted drummers), the band signed with Epic Records. Originally called Mookie Blaylock, the group changed its name to Pearl Jam, and their debut, Ten, followed in the fall of 1991. With the Seattle scene (Nirvana, Soundgarden, Alice in Chains, et al.) exploding on the charts, airwaves, and media, Pearl Jam picked the perfect time to issue their debut, which eventually outsold all other Seattle bands, and made Pearl Jam one of the biggest groups of the '90s (other hit albums followed: Vs., Vitalogy, No Code, Yield, and Binaural).

Vedder also became involved in numerous politically charged causes: his band took Ticketmaster to court over high ticket prices, he supported presidential candidate Ralph Nader and environmental causes, and was pro-choice. He also made special appearances at numerous concerts of bands he admirers (Bob Dylan's 50th B-day bash at Madison Square Garden, the Tibetan Freedom Concert, Who/Pete Townshend gigs, etc.), and played drums at live shows with the band Hovercraft (his wife's band). With his hard-hitting and often confessional lyrical style and Jim Morrison-esque baritone, Vedder also became one of the most copied lead singers in all of rock. Despite all the accolades, it wasn't until 2007 that Vedder released his first solo project, Into the Wild, the soundtrack to the Sean Penn film of the same time.

Following Pearl Jam's 2009 album Backspacer and its accompanying tour, Eddie Vedder released his first non-soundtrack album, 2011's Ukulele Songs, which included a mixture of covers and originals, with Vedder singing and accompanying himself on ukulele.