In 2003, he started hosting a weeknight radio show on WEDR.

During his career, Khaled has used many monikers including Arab Attack (discontinued soon after September 11 attacks), Big Dog Pitbull, Terror Squadian (used during his time with the hip-hop group Terror Squad), Beat Novacane (a moniker under which he produces beats), The Don Dada, Mr. The moniker Arab Attack which he used for music like "attack with music" was soon discontinued by him after September 11 attacks since he felt that using the moniker would seem disrespectful and offending towards those who suffered due to the 9/11 attacks.

He took up work in a local recording store which helped to lay foundations for his music career.

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That year, Khaled won two Ozone Awards: one for Best Video ("We Takin' Over") and another for Best Radio DJ.

In 2008, Khaled's third album We Global came out with singles "Out Here Grindin" with Akon, Rick Ross, Lil' Boosie, Trick Daddy, Ace Hood, and Plies, followed by "Go Hard" featuring Kanye West and T-Pain.

In 2006, Khaled released his debut album Listennn... He went on to release We the Best (2007), We Global (2008), Victory (2010), We the Best Forever (2011), Kiss the Ring (2012) and Suffering from Success (2013).

In 2009, Khaled became the president of record label Def Jam South and he is also the CEO and founder of We the Best Music Group.

DJ Khaled announced the title of the album, We the Best Forever, on Twitter. The first single released was "Take It to the Head" featuring Chris Brown, Rick Ross, Nicki Minaj and Lil Wayne. It's more than a crush." On July 29, 2013, in an interview with Funkmaster Flex, Minaj denied Khaled's proposal, saying: "Khaled is my brother and Khaled was not serious with that damn proposal, ya'll. He was kidding." The same day, Flex premiered Khaled's new single, titled "I Wanna Be with You" which featured Minaj, as well as frequent collaborators Future and Rick Ross.

On August 19, Khaled signed to Cash Money Records along to Universal Motown, the album will be released under the label, also under E1 Entertainment, Terror Squad, Def Jam South, and Khaled's own label We the Best Music Group, with confirmed guests as Fat Joe, Chris Brown, Keyshia Cole, Cee Lo Green, Cool & Dre, Rick Ross, Kanye West, Jay-Z, Nas, Birdman, Lil Wayne, T. The second single released was "I Wish You Would" featuring Kanye West & Rick Ross. The third official single was "Bitches and Bottles" featuring T. In January 2013, DJ Khaled announced that he had already started working on his seventh album and that it was titled Suffering from Success. This lead some to believe that his proposal was a "publicity stunt" to promote his new single.I., Akon, Drake, and Nicki Minaj The first single titled "Welcome to My Hood", featuring Rick Ross, Plies, Lil Wayne and T-Pain was released in January 13 of 2011, which was produced by The Renegades, and co-produced by DJ Khaled himself and The Nasty Beatmakers. After going to a doctor due to a bald spot on his beard the doctor told him he was "suffering from success" which inspired the album title. On April 28, 2014, DJ Khaled announced in an interview with MTV that Jay Z will be featured on his new single.The song is the first released under Cash Money Records and Universal Motown, Guests on the album are T-Pain, French Montana, Future, Wiz Khalifa, Nas, Plies, Ace Hood, Kanye West, Rick Ross, Meek Mill, Big Sean, 2 Chainz, Jadakiss, Kirko Bangz, Mack Maine, Tyga, T. The first single from the album is titled, "No New Friends" and features Drake, Lil Wayne and Rick Ross, along with production coming from Boi-1da and Noah "40" Shebib. The interview was noted due to Khaled "cursing, gesturing, and tossing the microphone to the floor in an effort to convey the importance and impact of the music he has coming this summer." A few hours after that, he released the single called "They Don't Love You No More", also featuring frequent collaborators Rick Ross, Meek Mill and French Montana.One of his first jobs was at the New Orleans record store Odyssey where he met both Birdman and Lil Wayne in 1993.After leaving Odyssey, he began DJing in reggae soundclashes, mixing dancehall and hip-hop. Soon after that, he started co-hosting with 2 Live Crew’s Luther Campbell on Campbell's WEDR radio show The Luke Show in 1998.We the Best (2007) is his second album with singles "I'm So Hood" with T-Pain, Trick Daddy, Plies, and Rick Ross and "We Takin' Over" with Akon, T. "We Takin' Over" peaked at number 28 on the US Billboard Hot 100 and number 11 on the US Hot Rap Tracks chart and was certified Gold by the Recording Industry Association of America on November 20, 2007.