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Born in South Jamaica, Queens, Jackson began drug dealing at the age of twelve during the 1980s crack epidemic. After leaving drug dealing to pursue a rap career, he was shot at and struck by nine bullets during an incident in 2000. After releasing his album Guess Who's Back? in 2002, Jackson was discovered by rapper Eminem and signed to Interscope Records. With the help of Eminem and Dr. Dre, who produced his first major commercial successes, Jackson became one of the world's highest selling rappers. In 2003, he founded the record label G-Unit Records, which signed several successful rappers such as Young Buck, Lloyd Banks, and Tony Yayo.

Jackson has engaged in feuds with other rappers including Ja Rule, Nas, Fat Joe, Jadakiss, Cam'ron, Puff Daddy, Rick Ross, and former G-Unit members The Game and Young Buck. He has also pursued an acting career, appearing in the semi-autobiographical film Get Rich or Die Tryin' in 2005, the Iraq War film Home of the Brave in 2006, and Righteous Kill in 2008. 50 Cent was ranked as the sixth best artist of the 2000�2009 decade by Billboard magazine. The magazine also ranked him as the fourth top male artist and as the third top rapper behind Eminem and Nelly. Billboard magazine also ranked him as the sixth best and most successful Hot 100 Artist of the 2000�2009 decade and as the number one rap artist of the 2000�2009 decade. Billboard ranked his album Get Rich or Die Tryin' as the twelfth best album of the 2000�2009 decade and his album The Massacre as the 37th best album of the 2000�2009 decade. As of September 2011, 50 Cent is working on his yet-to-be-titled fifth studio album, which is set to be released in November 2011.

Following time spent in a correctional boot camp, Jackson adopted the nickname "50 Cent" as a metaphor for "change". The name was derived from Kelvin Martin, a 1980s Brooklyn robber known as "50 Cent". Jackson chose the name "because it says everything I want it to say. I'm the same kind of person 50 Cent was. I provide for myself by any means".

On May 24, 2000, Jackson was attacked by a gunman, alleged to be Darryl "Hommo" Baum, outside his grandmother's former home in South Jamaica, Queens. He went into a friend's car, but was asked to return to the house to get jewelry. His son was in the house, while his grandmother was in the front yard. Upon returning to the back seat of the car, another car pulled up nearby. An assailant then walked up to Jackson's left side with a 9mm handgun and fired nine shots at close range. He was shot nine times: in the hand (a round hit his right thumb and came out of his little finger), arm, hip, both legs, chest, and left cheek. The face wound resulted in a swollen tongue, the loss of a wisdom tooth, and a small slur in his voice. His friend also sustained a gunshot wound to the hand. They were driven to the hospital where Jackson spent thirteen days. Baum, the alleged shooter, was killed three weeks later. Baum was also Mike Tyson's close friend and bodyguard.