White was born in Grosse Pointe Farms, Michigan on December 10, 1974, to Walter Hackett White, Jr. and Catherine White. She grew up in the affluent Detroit suburb with her parents and older sister, Heather. She attended Grosse Pointe North High School and, according to one classmate, was "always the quiet, obviously artistic type, and she just kept very much to herself." While still in high school, she decided not to go to college and instead began to work at Memphis Smoke, a restaurant in downtown Royal Oak, with aspirations of becoming a chef. It was there that she first met budding musician John "Jack" Gillis, a fellow high school senior from a Detroit neighborhood known as Mexicantown, and they frequented the coffee shops, local music venues, and record stores of the area. They began dating and were eventually married on September 21, 1996. Gillis took her last name.

Throughout the 1990s, Jack worked as an upholsterer, but continued to moonlight in several bands, usually as a Drummer. According to them, on Bastille Day (July 14) of 1997, Meg first tried playing on Jack's drumkit. In Jack's words, "When she started to play drums with me, just on a lark, it felt liberating and refreshing. There was something in it that opened me up." The two then began calling themselves The White Stripes (because Meg favored peppermint candies) and soon played their first gig at the Gold Dollar in Detroit. In keeping live performances to three basic elements, Jack did the guitar and vocal work while she played drums.

Public records shows White was married to Jack White from 1996 to 2000, prior to the White Stripes' formation.

Jack and Meg presented themselves as siblings to an unknowing public, and keeping to a chromatic theme, dressed only in red, white, and black. They began their career as part of Michigan's underground, garage rock music scene. They played along with and opened for more established local bands such as Bantam Rooster, the Dirtbombs, Two Star Tabernacle, Rocket 455, and the Hentchmen, among others. In 1998, the band signed with Italy Records, a small and independent Detroit-based garage punk label of Dave Buick. The band released its self-titled debut album in 1999, and a year later the album was followed up by the cult classic, De Stijl. The album eventually peaked at number 38 in Billboard's Independent Albums chart. Even as their success as a band was mounting, their personal relationship was faltering, and they were divorced in 2000.

Meg calls herself "very shy", and has kept a very low public profile. Though publicly insisting they were siblings, public records emerged in 2001 that indicated that she and Jack were married in 1996, prior to the band's formation; they divorced in 2000, before The White Stripes ascended to international fame. In 2009, she married Guitarist Jackson Smith, son of Musicians Patti Smith and Fred "Sonic" Smith. They divorced in 2013.

As the White Stripes fame spread beyond Detroit, the unconventional band with no bass player and a novice Drummer began to be the subject of mixed commentary among critics and fans. Of a 2002 concert in Cleveland, Ohio, Chuck Klosterman said, "[Meg] never grimaced and didn't appear to sweat; yet somehow her drums sounded like a herd of Clydesdales falling out of the sky, one after another. Clearly this is a band at the apex of its power." The Australian called her drumming "simplistic but occasionally explosive," and UK periodical, The Times said that she "reduced the art of drumming to its primary components, bashing the snare and cymbal together on alternating beats with the bass drum in a way that recalled Moe Tucker of the Velvet Underground." On the other hand, the Associated Press called her playing "maddeningly rudimentary." The satirical news site The Onion once featured the headline "Meg White Drum Solo Maintains Steady Beat For 23 Minutes". In reference to her "primal" approach to drumming, she remarked, "That is my strength. A lot of drummers would feel weird about being that simplistic." For his part, Jack has declared her drumming to be the "best part of this band," and called her a "strong female presence in rock and roll." He called her detractors "sexist".

White has also appeared on the cover of Whirlwind Heat's single "Pink", in a Detroit Cobras music video "Cha Cha Twist" as Little Red Riding Hood, and appeared with Jack White in a segment of Jim Jarmusch's 2003 film Coffee and Cigarettes.

White began with a red Ludwig Classic Maple kit that had a red and white peppermint swirl on the resonant heads of the toms and bass drum. On the Icky Thump tour, the bass drum head design was switched to a button. While recording From the Basement: The White Stripes, the design was switched to an image of White's hand holding the apple from the Get Behind Me Satan cover. Beginning in 2006, she also used a pair of Paiste 14" Signature Medium Hi-Hats, a 19" Signature Power Crash, and a 22" 2002 Ride. Meg also used Remo and Ludwig drumheads, various percussion instruments and Vater drumsticks.

In the summer of 2007, before a show in Southaven, Mississippi, Ben Blackwell (Jack's nephew and the group's archivist) says that Meg approached him and said, "This is the last White Stripes show." He asked if she meant of the tour, but she responded, "No. I think this is the last show, period." On September 11, 2007, the White Stripes announced via their website that they were canceling 18 tour dates due to Meg's acute anxiety. The following day, the duo cancelled the remainder of their 2007 UK tour dates as well.

In May 2009, White married Guitarist Jackson Smith, son of Musicians Patti Smith and Fred "Sonic" Smith. The wedding took place in Nashville, Tennessee, in a small ceremony in Jack White's backyard. White and Smith divorced in July 2013. As of 2014, White resides in Detroit, Michigan.

However, almost two years passed with no new releases, and on February 2, 2011, the band reported on their official website that they were disbanding. The statement emphasized that it was not due to health issues or artistic differences, but "mostly to preserve what is beautiful and special about the band."

White's Pearl Export bass drum—complete with original peppermint-painted bass drum that she used with the band's first show—and the Pearly Queen outfit she wore in the photos for the Icky Thump album, were featured in the Rock and Roll Hall of Fame "Women Who Rock" exhibition. In 2009, White donated her Ludwig kit to the Jim Shaw Rock 'N' Roll Benefit, an auction to raise money for the Detroit musician who was suffering from cancer.