Sheryl Suzanne Crow was born in Kennett, Missouri on February 11, 1962, to parents Wendell, a trumpet player and lawyer, and Bernice Crow, a piano teacher. The third child of the family, she has three siblings: older sisters Kathy and Karen and younger brother Steven.
While studying at Kennett High School, Crow was a majorette and an All-State track athlete, medaling in the 75-meter low hurdles. She also joined the Pep Club, the National Honor Society, Future Farmers of America, Freshman Maid, Senior Maid and Paperdoll Queen. She then enrolled at the University of Missouri, in Columbia, and received a Bachelor of Arts degree in Music Composition, Performance and Education. While in college, Crow sang in a local band, Cashmere. She was a member of the Kappa Alpha Theta social sorority, Sigma Alpha Iota women's music fraternity, and the Omicron Delta Kappa Society. Later, Crow was awarded an honorary doctorate from the Southeast Missouri State University, in Cape Girardeau, Missouri.

After graduating from college, Crow worked as a music teacher at the Kellison elementary school, in Fenton, Missouri. Teaching during the day allowed her the opportunity to sing in bands on weekends. Later, she was introduced to local musician and producer Jay Oliver. He had a thriving studio in the basement of his parents' home, in St. Louis, and helped her by using her in advertising jingles. Her first jingle was a back-to-school spot for the St. Louis department store Famous-Barr. McDonald's and Toyota commercial jingles soon followed. She was quoted in a 60 Minutes segment as saying she made $40,000 on her McDonald's commercial alone.

She toured with Michael Jackson during the BAD world tour from 1987-1989 and sang with him during the performance of "I Just Can't Stop Loving You." She also sang in the short-lived, infamous Steven Bochco drama, Cop Rock, in 1990.

In 1992, Crow recorded her first attempt at her debut album with Phil Collins' producer Hugh Padgham. The self-titled debut album was slated to be released on September 22 1992, but was ultimately rejected by her label. However, a handful of cassette copies of the album were leaked along with press folders to be used for album publicity. This album has been widely dispersed via file sharing networks and fan trading over the years. In the meantime, Crow's songs were recorded by major artists such as Celine Dion and Wynonna Judd.

She then began dating Kevin Gilbert and joined him in an ad hoc group of musicians known to everyone in the group as the "Tuesday Music Club". Group members, Gilbert, David Baerwald and David Ricketts (both formerly of David & David), Bill Bottrell, Brian MacLeod and Dan Schwartz share songwriting credits with Crow on her debut album, Tuesday Night Music Club.

The group existed as a casual songwriting collective prior to its association with Crow, but rapidly developed into a vehicle for her debut album after her arrival. Her relationship with Gilbert became acrimonious soon after the album was released, and disputes arose about songwriting credits. In later interviews, Crow claimed to have written all of the songs, but both Gilbert and Baerwald castigated Crow publicly, although Baerwald would later soften his position. A similar tension would arise with Bill Bottrell after her second album, over which he collaborated, at least in the early stages.

Tuesday Night Music Club went on to sell more than 7 million copies in the US and UK during the 1990s. The album also won Crow three Grammy Awards, in 1995: Record of the Year, Best New Artist and Best Female Vocal Performance.

Crow appeared in the "New Faces" section of Rolling Stone in 1993. The album featured many of the songs written by Crow's friends, including the second single, "Leaving Las Vegas". The album was slow to garner attention, until "All I Wanna Do" became an unexpected smash hit in the spring of 1994. As she later stated in People, she found an old poetry book in a used book store in the L.A. area and used a poem as lyrics in the song. To their credit, she and then-collaborator Bill Bottrell tracked down the author, Wyn Cooper, and he ended up being paid royalties on the song. The singles "Strong Enough" and "Can't Cry Anymore" were also released, with the former charting at #5 on Billboard and the latter hitting the Top 40. Crow received several Grammy awards in 1994: Best Female Pop Vocal Performance for "All I Wanna Do"; Record of the Year for "All I Wanna Do"; and Best New Artist. She performed at the 1994 and 1999 Woodstock Festivals, as well as the Another Roadside Attraction in 1997.

Crow supplied background vocals to the song "The Garden of Allah" from Don Henley's 1995 album Actual Miles: Henley's Greatest Hits. In 1996, Crow released her self titled second album. The album had songs about abortion, homelessness and nuclear war. The debut single, "If It Makes You Happy", became a radio success and netted her two Grammy awards for Best Female Pop Vocal Performance and Best Rock Album. Other singles included "A Change Would Do You Good", "Home" and "Everyday Is A Winding Road". Crow produced the album herself. The album was banned from sale at Wal-Mart; in "Love Is A Good Thing," Crow suggests that guns sold by Wal-Mart too easily fall into the hands of children.

In 1997, Crow contributed the theme song to the James Bond film, Tomorrow Never Dies. Her song Tomorrow Never Dies was nominated for a Grammy Award and Best Original Song Golden Globe. Crow collaborated on Scott Weiland's 1998 album, 12 Bar Blues.

In 1998 Crow released The Globe Sessions. During this period, she discussed in interviews having gone through a deep depression, and there was speculation about a brief affair with Eric Clapton. The debut single from this album, "My Favorite Mistake", was rumored to be about him, although Crow claims otherwise about a philandering ex-boyfriend. Crow has refused to say who the song was about telling Billboard Magazine on the release of her album. "Oh, there will be just so much speculation, and because of that there's great safety and protection in the fact that people will be guessing so many different people and I'm the only person who will ever really know. I'm really private about who I've had relationships with, and I don't talk about them in the press. I don't even really talk about them with the people around me." Despite the difficulties in recording the album, Crow told the BBC in 2005 that: "My favorite single is 'My Favorite Mistake'; it was a lot of fun to record and it's still a lot of fun to play." The album won Best Rock Album at the 1998 Grammy Awards. It was re-released in 1999, with a bonus track, Crow's cover of the Guns N' Roses song "Sweet Child o' Mine", which was included on the soundtrack of the film Big Daddy. The song won the 1999 Grammy for Best Female Rock Vocal Performance. Other singles included "There Goes the Neighborhood", "Anything But Down" and "The Difficult Kind". Crow won Grammy best female rock vocal performance for "There Goes the Neighborhood" in 2001.The Globe Sessions peaked at #5 on the Billboard 200 chart, achieving US sales of 2 million as of January 2008.

Later in 1998, Crow took part in a live concert in tribute to Burt Bacharach, in which she contributed vocals on One Less Bell To Answer, while wearing a full-length black formal dress.

In 1999, Crow also made her acting debut as an ill-fated drifter in the suspense/drama The Minus Man, which starred her then-boyfriend Owen Wilson as a serial killer. Shortly thereafter, she sported an unexpected short hairstyle.

She also released a live album called Sheryl Crow and Friends: Live From Central Park. The record featured Crow singing many of her hit singles with new musical spins and guest appearances by many other musicians including Sarah McLachlan, Stevie Nicks, the Dixie Chicks, Keith Richards and Clapton. "There Goes the Neighborhood" was included in the album, eventually winning the Grammy for Best Female Rock Vocal Performance. Crow also appeared on Return of the Grievous Angel: A Tribute to Gram Parsons, duetting with Emmylou Harris on the Parsons song, "Juanita".

Her fifth studio album Wildflower was released in September 2005. Although the album debuted at #2 on the Billboard charts, it received mixed reviews and was not as commercially successful as her previous albums. In December 2005, the album was nominated for a Best Pop Vocal Album Grammy, while Crow was nominated for a Best Female Pop Vocal Performance Grammy for the first single "Good Is Good". However, she ultimately lost in both categories to Kelly Clarkson. The album got a new boost in 2006 when the second single was announced as "Always on Your Side", re-recorded with British musician Sting and sent off to radio, where it was quickly embraced at Adult Top 40. The collaboration with Sting resulted in a Grammy-nomination for Best Pop Collaboration With Vocals. As of January 2008, Wildflower sold 949,000 units in the U.S.

In 2006, Crow contributed the opening track, "Real Gone", to the soundtrack for Disney/Pixar's animated film Cars. She also voices Elvis in the film. Crow was diagnosed with early-stage breast cancer in mid-February 2006. Her doctors have stated that "prognosis for a full recovery is excellent."

Crow's first concert since her cancer diagnosis was on May 18 in Orlando, Florida where she played to over 10,000 information technology professionals at the SAP Sapphire Convention. Her first public appearance was on June 12, when she performed at the Murat Theater in Indianapolis, Indiana.

The singer also appeared on Larry King Live on CNN on August 23, 2006. In this show she talked about her comeback, her breakup with Lance Armstrong, her past job as Michael Jackson's backup singer, and her experience as a cancer survivor.

In late 2006, Crow was nominated for a Golden Globe Award for the song "Try Not To Remember" (Best Original Song category) from the film Home of the Brave.

Crow wrote a foreword for the book Crazy Sexy Cancer Tips, author Kris Carr's book that was based on her 2007 documentary film Crazy Sexy Cancer. Crow contributed her cover of the Beatles's "Here Comes the Sun" on the Bee Movie soundtrack in November 2007. She contributed background vocals to the Ryan Adams song "Two" from the album Easy Tiger.