Peter Griesar was a bartender at Miller's beginning in 1989. In the August 1991, during Miller's annual respite for inventory, Matthews, Beauford, Moore and Lessard used the empty bar for rehearsing. Griesar heard the rehearsal, decided to take a break, and pulled out his harmonica and started playing with the band. After a few songs, he was invited to perform with them. He immediately accepted and became the band's first keyboardist.

Songwriter David John Matthews, working in Charlottesville, Virginia, as a bartender at Miller's bar in November 1990, became a friend of a Lawyer named Ross Hoffman. Hoffman convinced the usually reserved Matthews to record a demo of the few songs he had written. Hoffman hoped Matthews could shop the songs in order to find other Musicians to perform on some studio work with him. Hoffman encouraged Matthews to approach Carter Beauford, a local Drummer on the Charlottesville music scene. Beauford had been in several bands and was then playing on a jazz show on BET. After hearing Matthews' demo, Carter agreed to spend some time playing the drums, both inside and outside the studio. Matthews also approached LeRoi Moore, another local jazz musician who often performed with the John D'earth Quintet, to join them. Moore skeptically listened to the demo, but liked what he heard and decided that he too would give Matthews a chance. The trio began working on Matthews' songs in 1991. Matthews recollects that, "...the reason I went to Carter was not because I needed a Drummer, but because I thought he was the baddest thing I'd ever seen and LeRoi, it wasn't because I desperately wanted a saxophone, it was because this guy just blew my mind. At this jazz place I used to bartend at Miller's, I would just sit back and watch him. I would be serving the Musicians fat whiskeys and they'd be getting more and more hosed, but no matter how much, he used to still blow my mind. And it was the sense that everyone played from their heart. And when we got together and they asked, 'What do you want the music to sound like?' I said, 'I know this is a song I wrote and I like what you guys play, so I want you to play the way you react to my song.' There was a lot of breaking of our inhibitions."

The band's first in-studio demo was recorded in February or March 1991 prior to Tinsley joining as a full-time band member and consisted of "Song That Jane Likes", "Recently", "Best of What's Around", and "I'll Back You Up."

By the summer of 1991, they were playing at Eastern Standard with Charles Newman as their manager for a brief time. They also continued to play at fraternity functions; the last such show was at UVa at the DKE house on September 11, 1992. Thereafter the band began playing a regular Tuesday night show at the popular Charlottesville club Trax. Tapings of shows at Trax are some of the most widely shared among DMB fans. After Newman, Coran Capshaw, owner of the Flood Zone where the band often played, took the helm of the Dave Matthews Band.

On November 9, 1993, DMB released its first official release, Remember Two Things, on its Bama Rags label, later re-released by RCA in 1997. Live songs on the album were recorded at The Flood Zone in Richmond, Virginia on August 10, 1993, and The Muse Music Club on Nantucket Island on August 16–18, 1993. The album debuted on college charts as the highest independent entry, and went on to be certified platinum by the RIAA in 2002 — a significant accomplishment for an independent album. Meanwhile, the band kept touring and its fan base continued to grow. By allowing fans to tape shows for their personal use, DMB created a highly interactive community that continues to this day. Only recently has the band had to take legal action against some bootleggers who sell recordings of their concerts at a profit — something the DMB trading community also abhors.

On September 20, 1994, DMB released their debut studio album, Under the Table and Dreaming, featuring their first commercial hits "What Would You Say" (featuring John Popper of Blues Traveler fame on harmonica), "Satellite", and "Ants Marching". The album was dedicated "In memory of Anne" for Matthews' older sister Anne, who was killed by her husband in 1994 in a murder-suicide.

Known for their grassroots attitude and tight, engaging live shows, the Dave Matthews Band always encouraged fans to record its performances, and were one of rock's most bootlegged bands. In fact, a direct patch to the soundboard was made available to recordists until 1995, when some of these tapes found their way into less scrupulous, commercial-minded hands who, in the band's eyes, overcharged fans. The band cites college students trading these tapes in the early 1990s as a key reason for their current fame.

Under the Table and Dreaming and its follow-up album, Crash brought the band national attention, culminating in a Grammy Award for Best Rock Performance by a Duo or Group with Vocal for "So Much to Say" as well as four other nominations between the years 1996 and 1997. The band also achieved hits with "Crash into Me", "Too Much", and "Tripping Billies".

By 1997, DMB reached unparalleled levels of popularity across the United States and, to some degree, the world. On October 28, 1997, the band released their first full-length live album, Live at Red Rocks 8.15.95. The album, which was recorded at the Red Rocks Amphitheatre in Morrison, Colorado, featured popular songs from the band's first three albums and included longtime collaborator Tim Reynolds on electric guitar.

In an effort to promote fan interaction, the official fan association for DMB, Warehouse, was opened December 4, 1998. Warehouse gives fans early access to concert tickets, exclusive CDs and merchandise to its members. Warehouse Fan Association (also known as "The Warehouse") pioneered the internet-based ticket sales used by many artists today. DMB manager Coran Capshaw founded and ran Musictoday, a company which runs Warehouse and other online fan clubs. In August 2006, it was acquired by major concert promoter Live Nation, a spinoff of Clear Channel.

During the summer, the band took part in the Woodstock '99 concert and then released their third live album, Listener Supported, in the fall. The album, a live recording, used a show performed at the Continental Airlines Arena in East Rutherford, New Jersey on September 11, 1999 for a PBS television special. The album was also released as the band's first DVD. The year also provided two more Grammy nominations.

During 2000, DMB set up their own recording studio at a large countryside home outside Charlottesville. With longtime Producer Lillywhite at the helm, the band began work on a fourth studio album. The songs were heavily influenced by personal conflicts, notably the death of Matthews' uncle from alcoholism.

In March 2001, the Lillywhite conflict came full circle when the 2000 studio sessions with the Producer were leaked over the Internet. The tracks spread quickly over established Internet channels such as Napster. Collectively known as The Lillywhite Sessions, these tracks were lauded by both the fan base and the popular press. After critical comparison of the two simultaneous albums, fans that were less than pleased with Everyday's more electric sound were frustrated with the band's decision to scrap the work in exchange for Everyday.

Many of the songs from The Lillywhite Sessions would, however, eventually be officially released. In response to overwhelming fan support, coupled with a popular and widely publicized online campaign known as the Release Lillywhite Recordings Campaign, DMB returned to the studio in 2002 to record Busted Stuff. Produced by Stephen Harris, the recording Engineer who worked under Lillywhite on previous albums, the resulting CD provided new treatments of much of the Lillywhite Sessions' material, along with newly written songs "You Never Know" and the single "Where Are You Going" which was subsequently used in the movie Mr. Deeds. Busted Stuff hit the shelves on July 16, 2002.

On September 23, 2003, Some Devil, Dave Matthews first solo album was released and sold 469,000 copies in the opening week. The album's sinister lead single, "Gravedigger" won Matthews another Grammy Award. The album was followed by the Dave Matthews & Friends tour.

During March 2005, Dave Matthews Band arrived on Australian shores for the first time, playing shows in Melbourne, Sydney, Brisbane, and Byron Bay East Coast Blues & Roots Music Festival. Also in March, on the 9th, their tour bus driver, Stefan Wohl, plead guilty to charges of dumping the bus's waste tank into the Chicago river, onto a tour boat containing 109 passengers, on August 8, 2004.

The band supported the album with a 54 show, summer-long tour culminating in a four-night stand at Colorado's Red Rocks Amphitheatre. The 2005 summer tour also marked the first time Rashawn Ross played with the band. DMB also played a short, 13 show tour in the fall. This fall tour featured the return of Christmas Song, Minarets (both first played since 2003) and Linus and Lucy (last played in 2000).

The band worked with Reverb, a non-profit environmental organization, for their 2006 summer tour. Their Labor Day concert at The Gorge Amphitheatre drew a crowd of 64,468, the largest ever for that venue

On September 6, 2007, Dave Matthews Band performed a free concert for the Virginia Tech student body and faculty. The show was entitled "A Concert for Virginia Tech" and was done in memory of the shootings that took place on April 16, 2007. John Mayer, Phil Vassar, and Nas joined them. There were over 50,000 people in attendance. Two days later, they performed a benefit show at Atlanta's Piedmont Park with the Allman Brothers Band opening. Though only 65,000 tickets were sold (50,000 originally, then a second block of 15,000) nearly 20,000 people sneaked into the show, making it the largest one-day concert in Atlanta history. The show raised money for the Piedmont Park Conservancy Association. It was released as a CD/DVD called Live at Piedmont Park.

The Dave Matthews Band played their last show with all five original members on June 28 at the Nissan Pavilion in Bristow, Virginia. Two days later Saxophonist LeRoi Moore was injured in an ATV accident on his farm near Charlottesville, Virginia. On July 1, 2008 while in Charlottesville, Dave Matthews announced Moore's accident. Béla Fleck and the Flecktones Saxophonist Jeff Coffin filled in for Moore for the remainder of the tour. Although he was expected to make a full recovery, Moore died suddenly of complications from the accident on August 19. The following statement was released on the band's website

The band's next album, titled Big Whiskey and the GrooGrux King, was released on June 2, 2009, coinciding with a supporting summer tour, slated to run through early October. The band named this album in honor of Moore. Moore is said to be the "King" in the album title. Tim Reynolds, Rashawn Ross and Jeff Coffin performed with the band on both the spring and the summer tours of 2009 and 2010.

According to the band's website, as of May, 2010, the band's own charity, the BAMA Works Fund, has contributed over $8.5 million to a wide variety of need organizations. It was founded in 1999 to address the needs of disadvantaged youth, disabled persons, the environment, and arts and humanities in the city of Charlottesville, Virginia area, and surrounding area of Albemarle, Buckingham, Fluvanna, Greene, Louisa, Nelson, and Orange Counties. In addition, BAMA Works Fund has been active in other projects, and often the Dave Matthews Band, both as a whole and individually, have planned charity events and donated their time and resources outside of Charlottesville. Some examples include building a "Village Recovery Fund" after the tsunami that ravaged Sri Lanka, promoting a challenge grant for the Habitat for Humanity Musician's Village in New Orleans, multiple appearances to benefit both Farm Aid and the annual Neil Young-sponsored Bridge School Benefits, fundraisers for the victims of Hurricane Katrina, and followed this with donations after the 2010 disaster that leveled many villages in Haiti. The band played benefit concerts to help fund the school system in New York City, and countless other concerns. As a result, the band was awarded the NAACP Chairman's Award. In Matthews' acceptance speech, he spoke for the band as a whole, commenting that of all the achievements they had enjoyed, that the award by the NAACP and Julian Bond in particular was by far the highest honor they had bestowed upon them.

On December 16, 2011, the band officially released the Dave Matthews Band Caravan show that took place on June 26, 2011 as Live at Atlantic City.

Following the successful release of Away from the World, the band kicked off their 15 show, 2012 Winter Tour with a two-night show in East Rutherford, New Jersey on November 30 and December 1, 2012. The show that took place on November 30, featured the band playing every song off Away from the World. This marks the first time that the band has played an album in its entirety at a single show. Shows from November 30 to December 9 were opened by Jimmy Cliff while the second half of the shows on the tour (from December 11 to December 22), were opened by The Lumineers. They concluded the tour at the Wells Fargo Center in Philadelphia on December 22, 2012 where he still played 6 songs from his new album, Away From the World.

In November 2013, Matthews announced that a new album was in the works. The record will be produced by Rob Cavallo.

In September 2014, it was announced that Dave and Tim would be kicking off the year with a two night stand in Oakland, California, at the historic Paramount Theatre (Oakland, California) on January 16 and January 17.

The band debuted three new songs, May 7, 2015, the band debuted Black and Blue Bird, on Legends on Letterman, and at a summer tour show in Raleigh, North Carolina on May 22, 2015, the band debuted Be Yourself with additional accompaniment guests, the Lovely Ladies. On June 12, 2015, Virginia in The Rain was debuted at Hartford, Connecticut.

In June 2016, the band announced that a CD set of Dave Matthews' 1996 solo performance at Sweet Briar College would be released later on in the summer, with all profits to be donated to the college, which almost closed in 2015.

On February 2, 2018, Boyd Tinsley announced he is taking an indefinite break from the band to focus on family and health.

Their limited instrumentals, however, did not provide the full sound they desired; more Musicians were needed. John D'earth, Conductor of the University of Virginia orchestra and a local musician, taught music at the Tandem Friends School and had previously played alongside Moore and Beauford in the jazz fusion band "Secret". Stefan Lessard, a junior Bassist at the time, was under his guidance in a student jazz combo known as "Yabanci Jazzites". On the recommendation of John D’earth, the 15-year-old Lessard was asked to join in the studio to help complete the demo. While the partnership was never intended to continue beyond the studio, the four liked the sound and decided to continue together for live performances as well. Consequently, regular practices began in the basement of Carter Beauford's and Matthews' mother's home.