JoJo was born in Brattleboro, Vermont, but raised in Keene, New Hampshire, and Foxborough, Massachusetts. She has Native American, Irish, Polish and French family background. She grew up in a one-bedroom apartment in Foxborough in a low-income family. Her father, Joel Maurice Levesque (January 8, 1955 – November 14, 2015), sang as a hobby, and her mother, Diana Levesque (née Blagden) sang in a Catholic church choir and was trained in musical theater. JoJo's parents divorced when she was four years old, and she was raised as an only child by her mother. JoJo's stage name comes from a childhood nickname.

At age seven, JoJo appeared on the television show Kids Say the Darndest Things: On the Road in Boston with American Comedian and actor Bill Cosby, and she sang a song from singer Cher. After auditioning in the television show Destination Stardom, JoJo sang Aretha Franklin's 1967 hit "Respect" and "Chain of Fools". Soon after, The Oprah Winfrey Show contacted her, inviting her to perform. She performed on Maury, on one of the "kids-with-talent" episodes, as well as many others. Reminiscing, she has stated that "when it came to performing, I just had no fear."

At six years old, JoJo was offered a record deal, but her mother turned it down because she believed JoJo was too young for a music career. After appearing on various talk shows, the McDonald's Gospelfest, performing Whitney Houston's "I Believe in You and Me" and competing on the television show, America's Most Talented Kids (losing to Diana DeGarmo), record Producer Vincent Herbert contacted her and asked her to audition for Blackground Records. During her audition for Barry Hankerson, Hankerson told her that the spirit of his niece, the late singer Aaliyah, had brought her to him. She was signed to the label, and had recording sessions with producers The Underdogs and Soulshock & Karlin. JoJo's live demo, Joanna Levesque, recorded in 2001, features covers of soul and R&B songs, including Wilson Pickett's 1966 "Mustang Sally", Etta James's 1989 "It Ain't Always What You Do (It's Who You Let See You Do It)", Aretha Franklin's 1968 "Chain of Fools" and 1969 "The House That Jack Built", The Moonglows' 1956 "See Saw", Stevie Wonder's 1972 "Superstition", and The Temptations' 1975 "Shakey Ground".

In addition to her music career, JoJo also launched a career in acting. She made guest appearances on several television series, beginning with the 2002 American sitcom The Bernie Mac Show, and later in American Dreams in 2004 and Romeo! in 2006. That same year, JoJo made her feature film debut in two Hollywood films Aquamarine and RV. She starred in the Lifetime Television film True Confessions of a Hollywood Starlet in 2008.

In 2003, at age 12, JoJo signed with Blackground Records and Da Family and began working with producers for her first album. JoJo's gold-certified debut single "Leave (Get Out)" was released in 2004. Before the album's release, JoJo embarked on her first ever tour, the Cingular Buddy Bash with pop rock singer Fefe Dobson, hip hop duo Young Gunz, alternative metal band Zebrahead, and teen pop stars Ryan Cabrera and Busted. Like debut tours by Tiffany and Britney Spears before her, it stopped at nine malls, starting at Atlanta's Northlake Mall and ending at South Shore Plaza near her hometown of Foxborough. When the single reached number one on the Top 40 Mainstream, she became, at age thirteen, the youngest solo Artist to have a number-one single in America. The first single was nominated for Best New Artist at the 2004 MTV Video Music Awards, which made JoJo the youngest MTV Video Music Award nominee. Her first album, the platinum-selling JoJo, was released in 2004, peaking at number four on the U.S. Billboard 200 and number ten on the Top R&B/Hip-Hop Albums, selling 95,000 copies in its first week and reaching the top forty of the UK Albums Chart. In December 2004, she was nominated for Female New Artist of the Year and Mainstream Top 40 Single of the Year at the Billboard Music Awards. She is also the youngest Artist to be nominated at the Billboard Music Awards. Her second single, released in September 2004, the gold-selling "Baby It's You" – which features Rapper Bow Wow – peaked at number twenty-two in the U.S. and number eight in the UK. The final single from the album, "Not That Kinda Girl", was released in 2005 and peaked at number eighty-five in Germany.

Upon making her mainstream debut in 2004, critics immediately noticed that JoJo's vocal prowess and material exceeded her age. When she released her single "Demonstrate" in 2012, critics observed that both the singer's voice and lyrics had matured alongside her. Subsequently, JoJo's second mixtape Agápē drew attention from both critics and the singer's own family due to its mature content; Agápē features lyrical references to drinking, drug abuse and sex, which were absent from her previous "G-rated" releases. The mixtape also addresses her conflict with her record label. JoJo's early image followed popular trends related to hip hop culture at the time. The cover of JoJo's first album features the singer donning a T-shirt and cap, which Sal Cinquemani of Slant Magazine dismissed as "contrived and calculated". Matt Collar of AllMusic wrote, "Jojo is an assured and likeable performer who can somehow embody the yin-yang persona of a suburban Cheerleader slinging hip-hop attitude." According to Jenny Eliscu of Rolling Stone, the singer "has become a role model to suburban adolescents who talk gangsta but still carpool to school in mom's Kia Sorento."The Guardian's Alex Macpherson commented that "In an era of boozy Amys, gobby Lilys and flashing Britneys, a pop star as wholesome as JoJo seems almost quaint." Writing for Prefix, Norman Meyers believes that JoJo "could have been a Mean Girls extra, but she has talent" and "comes off more like a pint-size Mariah Carey or Christina Aguilera than a hip-shaking Britney clone".

JoJo dated American soccer player Freddy Adu from May 2005 until September 2006. The couple met on the MTV show Fake ID Club while JoJo was hosting it. JoJo made an appearance in the commentary box at a New England Revolution home game when they were playing D.C. United. In November 2006, The Washington Post reported that the couple had split up. JoJo revealed on American Top 40 with Ryan Seacrest that she and Adu were still good friends.

In 2006 JoJo was cast opposite Emma Roberts and Sara Paxton in Aquamarine, playing Hailey. The film opened on March 3, 2006, opening at number five with $7.5 million. Her second major film, RV, a comedy starring Robin Williams, was released on April 28, 2006. It opened at number one and grossed $69.7 million. JoJo had to audition for the part five times, and eventually replaced an Actress who had already been cast in the role. JoJo's second album, The High Road, was released on October 17, 2006. The album debuted at number three on the Billboard 200, selling 108,000 units. It was produced by Scott Storch, Swizz Beatz, J. R. Rotem, Corey Williams, Soulshock & Karlin and Ryan Leslie. It received mainly positive reviews. In the summer of 2006, the lead single from her second album, "Too Little Too Late", was released to radio stations. "Too Little Too Late" broke the record for the biggest jump into the top three on the Billboard Hot 100 chart, moving from number 66 to number three in one week; this record was previously held by Mariah Carey with her 2001 single "Loverboy", which went from number 60 to number two. The album's second single, "How to Touch a Girl", experienced less success. It charted just outside the Billboard Hot 100 and peaked at number 76 on the Billboard Pop 100. "Anything", was released as a third single to little success. The album sold over 550,000 copies and was certified gold by the RIAA in December 2006.

On July 20, 2007, JoJo's version of "Beautiful Girls" by Sean Kingston leaked on the internet titled "Beautiful Girls Reply". It debuted at number thirty-nine on the Billboard Rhythmic Top 40 chart one month later. In late 2007, JoJo stated that she would be writing songs for her third album, to be released when she turned 18. She said she wanted her fans to "see growth" in her music.

In late 2009, JoJo appeared on Timbaland's Shock Value II as a featuring Artist on the song "Lose Control". She later appeared on "Timothy Where You Been" with the Australian band Jet as a background vocalist. On September 10, JoJo revealed that she would be traveling to Toronto to film a small screen adaptation of Lola Douglas' True Confessions of a Hollywood Starlet and play the role of Morgan Carter, with Valerie Bertinelli and Shenae Grimes. It was broadcast on Lifetime Television on August 9, 2008, and released on DVD on March 3, 2009.

In August 2009, JoJo graduated from high school and stated that she would stay focused on Future projects. She was accepted to Northeastern University but did not attend; she considered majoring in cultural anthropology.

Can't Take That Away from Me was released as JoJo's first mixtape in September 2010 and spawned the single "In the Dark". In late 2010, JoJo made cameo appearances in music videos for Keri Hilson and Clinton Sparks. In January 2011, JoJo was cast in an episode of CBS's Hawaii Five-0 as Courtney Russell, the daughter of a Tsunami Warning Center scientist who goes missing on the eve of a big storm hitting the Honolulu coast. In February 2011, JoJo uploaded a video to YouTube announcing that she was shooting a video for a new song, titled "The Other Chick" and that she had changed the title of the album from All I Want Is Everything to Jumping Trains, stating that she had desires to "represent something different; something fresh". Her actual first lead single "The Other Chick" was supposed to release digitally but the label decided to make it as a buzz single and the decision for a lead single is still in hold. In June 2011, she released a remix of Rapper Drake's song "Marvin's Room", renamed "Marvin's Room (Can't Do Better)" through Rap-Up's YouTube channel. JoJo rewrote the song from a female perspective to express a frustration towards an ex-lover and his supposed new girlfriend. Drake himself expressed his appreciation for her interpretation.

On August 29, 2011, "Disaster" was released to U.S. radio. The song saw her continue in a similar style to her previous hits, which was praised by critics for not "jumping on the synthpop bandwagon", but also criticized for not showing much progression after a five-year hiatus. "Disaster" debuted on the Billboard Hot 100 at number 87, but fell off the chart the next week. This gave JoJo her first charting single since "Too Little Too Late" in 2006. The single failed to impact any chart internationally. In support of the single, she opened for the Joe Jonas & Jay Sean Tour. JoJo gave her first televised performance of the song on Good Day Dallas on September 29, and later performed on a small promotional tour for "Pinktober" in order to raise money for breast cancer research during the month of October. A music video for the song premiered on JoJo's website in November 2011. In August 2011, JoJo signed a promotional deal with HeartSoul clothing to become the new face for their Fall/Winter collection. In December 2011, JoJo signed a deal with skin care brand Clearasil to become the new spokeswoman for Clearasil's PerfectaWash.

After Blackground Records lost their distribution deal through Interscope Records in late 2012, resulting once again in the delay of the release of an album, JoJo began recording new material specifically for a new mixtape to be released by the end of the year, as she "didn't want to keep the fans waiting for new music any longer". On November 15, 2012, she announced the release of a mixtape, titled Agápē, which means "unconditional love" in Greek. The project was released for free through digital download on her 22nd birthday on December 20, 2012. In support of the mixtape, JoJo embarked on her first headlining North American tour, The Agápē Tour. "We Get By", was released as the lead single from the mixtape on November 15, 2012. "André" was released as the second single from the mixtape on November 30, 2012, with the music video for the song premiering on March 21, 2013 through Complex magazine.

On July 30, 2013, it was reported that JoJo had filed a lawsuit against her labels Blackground Records and Da Family for "irreparable damages to her professional career". Minors cannot sign contracts that last more than seven years under New York State law and thus she claims that as her contract was signed in 2004, her deal should have expired in 2011. In December 2013 both of JoJo's and Blackground's attorneys agreed to drop the case as both parties came to an agreement outside court. On January 14, 2014, it was announced that JoJo was released from her multi-year battle with the label and signed a new recording contract with Atlantic Records. On February 14, she released an extended play, titled #LoveJo, featuring covers of three classic songs, which were all produced by Da Internz. On March 16, 2014, she performed at SXSW.

On August 5, 2015, JoJo's website under Atlantic was relaunched. On August 20, 2015, JoJo released three singles simultaneously on the III. extended play, which she referred to as a "tringle", as a preview of her third studio album. In support of the release, JoJo embarked on the I Am JoJo Tour, her first world tour, in November 2015. On December 18, 2015, JoJo released the sequel to "#LoveJo", titled #LoveJo2.

In June 2016, Fifth Harmony announced that JoJo would be one of the opening acts on their The 7/27 Tour. On July 27, 2016, JoJo released the lead single "Fuck Apologies", featuring Rapper and label mate Wiz Khalifa. Mad Love, JoJo's third studio album was released on October 14, 2016, ten years following the release of The High Road. The album entered and peaked the Billboard 200 Chart at number 6. In January 2017, JoJo embarked on the Mad Love tour, a four-month concert tour of North America and Europe.

In August 2017, JoJo announced her departure from Atlantic, in conjunction with announcing her new music venture, Clover Music, in a joint deal with Interscope.