Morales' work as a house music producer began in 1993, with a full 11-track album entitled The Program, released under the Phonogram Records label. "Gimme Luv (Eenie Meenie Miny Mo)" was the most successful single to be lifted from the debut LP and was a major dance hit - spending two weeks on top of the Billboard dance chart in August 1993.  After his debut release, Morales produced few original records, focusing instead on carving out his career as one of the first true "superstar" DJs and as a prolific remixer, working with some of the biggest names in music. In 1998, under the pseudonym David Morales presents The Face he released his biggest hit to date, "Needin' U".

Featuring samples from The Chi-Lites' "My First Mistake" and Rare Pleasure's "Let Me Down Easy", the record became an overnight classic and introduced Morales into mainstream airplay.

Following up this success, in 2000 Morales offered up another overnight hit, "Higher", co-produced by Albert Cabrera, with vocals by Deanna Della Cioppa, and released under the pseudonym David Morales & Albert Cabrera present Moca. In November 2004, after an interval of 11 years, Morales released his second album, 2 Worlds Collide, a 10-track album released on Ministry of Sound's record label, Data Records.

The album is reminiscent of earlier house music mixed with current and progressive sounds. The release contained another big hit for Morales titled "How Would U Feel" which features vocals from Lea-Lorien. In addition to his work as a record producer, Morales is also part of the Def Mix collective, alongside long term partners Frankie Knuckles and Satoshi Tomiie, who produce both original productions and remixes.

Since 1986, Morales has also carved out a career as arguably one of the most in-demand remixers of the post-house era. He has worked with a large assortment of successful and famous artists, including Madonna, Kylie Minogue, Whitney Houston, Pet Shop Boys, Michael Jackson, Janet Jackson, U2, Luther Vandross, Aretha Franklin, Diana Ross, Jocelyn Brown, CeCe Rogers, the Spice Girls, and many others.

His first reworking of a Carey record was "Dreamlover" (1993) Morales worked with Carey at almost every stage of her career following "Dreamlover", re-working the songs "Fantasy" (1995), "Always Be My Baby" (1996), "Honey" (1997), "My All" (1998), "I Still Believe" (1999), "It's like That" (2005) and "Say Somethin'" (2006) into number-one hits on Billboard's Hot Dance Club Play chart in the U.S.  Morales was awarded the 1998 Grammy Award for Remixer of the Year, Non-Classical.

David Morales is considered by many to be one of the first so-called superstar DJs.  Larry Levan was the first to recognise the potential for success in Morales, and he was soon a popular regular at The Loft, Paradise Garage and The Sound Factory - all highly influential New York City nightclubs in the late 1980s and early 1990s. His remix and production work helped him expand his DJ career, allowing him to perform at major clubs around the globe including the Ministry of Sound in London. He also became one of Ibiza's most renowned DJs, appearing at venues such as Pacha.

In addition to his nightclub sets, Morales also contributed to a large number of radio mix shows throughout the 1990s, the most important being Hot 97's popular segment All-Night House Party. He also produced various DJ mixes for radio stations around the world, including London's KISS 100. Morales also contributed his DJ skills to a variety of compilations including Ministry of Sound's Sessions Seven, United DJs of America Volume 4 (a joint project with Def Mix partner Frankie Knuckles) and most recently with the retrospective collection Mix The Vibe: Past-Present-Future.

Besides his music career, Morales owned a nightclub called the Stereo nightclub located in Montreal, Quebec, Canada. Serving also as the club's resident DJ , he was well known for his sets including his 16-hour "La Vie en Stereo" sets, which occurred on the last Saturday of each month. Stereo nightclub closed in July 2008 after a fire but reopened with different owners in September 2009. David Morales returned to Stereo as a DJ in January 2011. In April 2006, he opened a short-lived nightclub called Sonic in Toronto, however due to unknown reasons, the club officially closed on March 10, 2007.

David Morales has also been involved in other projects unrelated to his music career. He is also credited for laying the groundwork and initial sketches that led to the design of Comic Sans.  In addition to his music career, he has served as a model for Italian clothing design house Iceberg.