In 1991, Benjamin Saleznow from The Source magazine praised him in his "Unsigned Hype" column that highlighted unsigned hip-hop artists. Later, he was signed to the Columbia Records subsidiary Ruffhouse in 1992; under that label he released his debut single "Born Loser", which did not get much airplay. However, Ruffhouse promoted many other artists on its roster rather than DMX and so agreed to release him from his contract eventually. In 1994, he released a second single, "Make a Move", followed by a guest spot on Mic Geranimo's "Time To Build" along with a young Jay-Z and Ja Rule.

In 1997, Simmons earned a second major-label shot with Def Jam, and made a successful guest appearance on LL Cool J's "4, 3, 2, 1." Additional guest spots on Mase's "24 Hours to Live" and "Take What's Yours", and The LOX's "Money, Power & Respect" created an even stronger buzz.

He has starred in Never Die Alone, which was based on street novelist Donald Goines' book. He is also set to star in three upcoming films. He was set to star in Marble City, but was replaced by Ving Rhames. He has finished filming another action thriller called Last Hour which should see a release at the end of 2008. He also had a reality show on BET called DMX: Soul of a Man. He will also star in the 2009 Beast, the sequel to Belly. He has finished shooting an upcoming film with Kris Kristofferson titled Lords of the Street, the release date has yet to be set. He can be seen starring alongside Clifton Powell & Vivica A. Fox in a film titled Father of Lies. In 2003 he starred in a movie called Cradle 2 the Grave, as a criminal father trying to save his daughter. In 2001 he starred in Exit Wounds as a thug Latrell Walker who uncovered a team of crooked cops along with Steven Seagal who was transferred to the roughest division in Detroit, division 15.