JoJo's self-titled debut album was released in June 2004 and has sold over 3 million copies worldwide. The first single off of the album, “Leave (Get Out)”, was released in February 2004. It peaked at #12 on the Billboard Hot 100, and was certified gold by the RIAA. JoJo's second album, The High Road, was released in October 2006, and has sold over 2 million copies worldwide. The album's lead single, “Too Little Too Late”, was released in August 2006 and reached number three on Billboard Hot 100. The single was certified with platinum by the RIAA.

The singer's first mixtape, Can't Take That Away from Me, was released exclusively to Rap-Up on September 7, 2010. The mixtape is a prelude to her upcoming third studio album All I Want Is Everything, which is scheduled for an early 2011 release through Blackground and Interscope Records. The first single from the Mixtape was “In the Dark” was released exclusively to Rap-up.com on August 30, 2010.

JoJo also has a film career. She made her first television appearance by The Bernie Mac Show. In 2006 She starred in two Hollywood films, Aquamarine, her first film debut and RV. She has hosted the Ultimate Prom, and appeared in the movie True Confessions of a Hollywood Starlet which earned her a nomination at the Poptastic Awards.

JoJo has acted since age four. She did local theater, radio, and TV commercials in the New England area, and national TV shows from age seven. JoJo made her professional stage debut at eight in Shakespeare's A Midsummer Night's Dream as Mustardseed at the Huntington Theater. She received her first union card from the American Federation of Television & Radio Artists (AFTRA) at ten.

After appearing on the television series The Bernie Mac Show and American Dreams, 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 stated that “no one hired an acting coach for me on the set of Aquamarine.” She announced that she will be billed as “Joanna 'JoJo' Levesque” in her film roles, but that she will still be credited as simply “JoJo” for her music work.

In 2005 she was offered a role as Zoe Stewart in the hit television series Hannah Montana on the Disney Channel, but she turned down the role because she was not really interested doing a television show. She was more concerned with being a legitimate artist, and a film career was not really what she saw for herself. On August 28, 2007, in an interview with BOP and Tiger Beat online, JoJo stated that she was working on a new film. 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 Golden Globe winner Valerie Bertinelli and 90210-star Shenae Grimes, to be broadcast on Lifetime television. The film was released on August 9, 2008 on Lifetime Television and on DVD on March 3, 2009.

According to rumors JoJo was offered the role of Jeanette Miller in the sequel to the film Alvin and the Chipmunks with Drew Barrymore and Miley Cyrus, but these rumors were refuted in 2009. Actress Christina Applegate got the role instead.