Loso was born John David Jackson on November 18, 1977, of African American and Dominican descent. He grew up in the Bedford-Stuyvesant neighborhood of Brooklyn, New York. While in high school in twelfth grade, Fabolous began to pursue a rap career. He was invited to rap live on DJ Clue's radio show and on WQHT Hot 97, where he was signed to Desert Storm Records. He was featured on several DJ Clue mixtapes and mixtapes with Roc-A-Fella artists. This earned Fabolous and Desert Storm a distribution deal with Elektra Records.
Before receiving mainstream popularity, Fabolous released a press statement confirming allegations of attempted murder before releasing his "coded" single in 1998 titled "If They Want It" under his moniker,"Fabolous Sport". It was released by Def Jam Recordings on the album DJ Clue? The Professional and as a bonus track on his debut album Ghetto Fabolous. It is also available on the DJ Kool Kid mixtape, Pound For Pound featuring Fabolous and Jadakiss. In 2000, he released a second single through Elektra Records titled "Gotta Be Thug", which was put on DJ Clue Presents Backstage Mixtape (soundtrack).
Fabolous released his debut album, Ghetto Fabolous, in September 2001. It debuted at number four on the Billboard 200, selling over 143,000 copies in its first week. The album's first single, "Can't Deny It", was produced by Rick Rock and features a chorus by Nate Dogg interpolating Tupac Shakur's song "Ambitionz Az a Ridah". It charted on the Billboard Hot 100, along with two of the subsequent singles. The other charting singles were "Young'n (Holla Back)", which is produced by The Neptunes and "Trade It All", which features vocals from Jagged Edge and is produced by DJ Clue and Duro.
In January and March 2003, Fabolous was arrested for possessing an unlicensed gun in his car. His bodyguard later showed proof of ownership for the gun. Fabolous put his career on hiatus for much of 2005 and 2006.
Fabolous was shot in his right leg on the morning of October 17, 2006 in Manhattan after exiting Justin's, a restaurant owned by Diddy. The police saw the rapper and three other men accompanying him rushing through a red light and found unlicensed, loaded guns in their car leading to their arrest. After they found the weapons, Fabolous was treated at a local hospital.