The child of a single mother, Simmons grew up in the inner city of Yonkers, New York. He began pursuing a career in hip-hop in the early 1990s, a 1994 deal with Columbia Records fell through. In the late 1990s, he joined the Ruff Ryders Entertainment management company, who arranged a deal with Def Jam for Simmons, who went by the stage name of "DMX" (The name of a beat machine that was popular when DMX first became a beat boxer, before entering rapping). DMX's debut single was "Get at Me Dog", an instant hit. His critically-acclaimed debut album, It's Dark and Hell Is Hot, is considered a classic hip-hop album, and is often credited with revitalizing Hardcore Rap in the mainstream scene, after Puff Daddy and Bad Boy Entertainment briefly dominated the charts with their pop-orientated and sample-reliant tunes. The album It entered the charts at #1 in 1998, as did its follow-ups Flesh Of My Flesh, Blood Of My Blood (also 1998), ...And Then There Was X (1999) and The Great Depression (2001). A number of hit singles kept DMX a presence on both urban and pop radio, including "Ruff Ryders Anthem" (1998), "Money, Cash, Hoes" (1998, with Jay-Z)", "Slippin'" (1999), "What's My Name" (1999), and "What These Bitches Want" (2000), featuring Sisq󠡮d produced by Sisq󧳠Dru Hill bandmate Nokio.

In September of 2003, DMX released his fifth album Grand Champ and became the only artist in the history of the Billboard 200 to reach No. 1 with his first five albums. His success paved the way for Ruff Ryders to establish a label of its own, signing Eve, Drag-On, Swizz Beats, and former Bad Boy Records artists The Lox to their Interscope Records-distributed imprint.

DMX also branched out into acting, appearing in the motion pictures Romeo Must Die with Aaliyah and Jet Li, Exit Wounds with Steven Seagal, Cradle 2 the Grave with Jet Li and Gabrielle Union, and Never Die Alone with Michael Ealy. Also starred in "Belly", featuring fellow rappers Method Man and Nas.

DMX also has a criminal history originating with an arrest in 1999 in Teaneck, New Jersey, when police found a pistol, crack pipes and 13 pit bulls on the premises of his home. He pleaded guilty to charges of animal cruelty, disorderly conduct and possession of drug paraphernalia, and was sentenced to make public service announcements for the Humane Society.

In June of 2004, DMX and a friend were arrested in the parking lot of Kennedy Airport in New York for allegedly attempting to steal a car and impersonating a federal agent. DMX was taken to central lockup in Queens and held on charges of attempted robbery, criminal impersonation and criminal mischief. He pleaded guilty to reckless endangerment in December and was sentenced to a conditional discharge. His driver's license was suspended for the incident and he had to forfeit his 1998 Ford Expedition.

In April of 2005, DMX was arrested in The Bronx for driving with a suspended license after his car crashed into a police cruiser.

In October of 2005, DMX was sentenced to 60 days in prison after pleading guilty to two traffic violations while his license was suspended, one being the incident in April and the other involving driving his car at 104 mph near his Westchester home.