Light heavyweight

Moorer had a fast rise through the professional boxing ranks. He debuted on March 4, 1988, knocking out Adrian Riggs in the first round. Before the year's end, he was undefeated in eleven bouts (winning all by way of early round knockouts) and fighting for the world title for the first time. He acquired the newly created WBO light heavyweight title with a five-round knockout of Ramzi Hassan.

In 1989, he retained the title six times, beating Freddie Delgado, Frankie Swindell, Mike Sedillo and former WBA champion Leslie Stewart, among others.

In 1990, he retained the title three times before the end of the year, beating Mario Melo and former Michael Spinks challenger Jim McDonald, among others.

Heavyweight

1991 saw Moorer move up to the heavyweight division. He rolled through the competition en route to securing an opportunity to fight for the vacant WBO heavyweight championship the following year against Bert Cooper. Moorer stopped Cooper in the fifth round after both fighters were down and hurt during the bout.

He did not defend the then-lesser regarded WBO heavyweight belt. Moorer and trainer Emanuel Steward parted ways after the Cooper fight. Moorer eventually joined Lou Duva's team, and was trained by Georgie Benton for three fights in 1993, including a 10-round decision win over former champion James "Bonecrusher" Smith.

Moorer then parted ways with the Duvas and Benton, and hired New York-based trainer Teddy Atlas in late 1993. Moorer closed the year with a ten-round decision over Mike Evans.

Unified heavyweight champion

On April 22, 1994, Moorer challenged Evander Holyfield for the lineal, IBF, and WBA title belts. In round 2 Holyfield sent Moorer down on the canvas, but Moorer overcame and went on to win a majority decision. As a result, he became the first-ever southpaw heavyweight champion.

In his first defense of those belts, on November 5, 1994, Moorer faced 45-year-old George Foreman, who lost his last fight for the vacant WBO heavyweight title to Tommy Morrison. For nine rounds, Moorer easily outboxed him, hitting and moving away, while Foreman moving forward, seemingly unable to "pull the trigger" on his punches. Moorer was ahead on all three judges' scorecards entering the 10th round, when Foreman hit him with a number of long-range jabs. Then, suddenly, a short right hand caught Moorer square on his chin, gashing open his bottom lip, and he collapsed to the canvas. Moorer was knocked out and lost the world championship. He also lost his undefeated record. Foreman, at age 45, became the oldest fighter ever to win the world heavyweight title.

The following year, Moorer re-grouped by winning against fringe contender Melvin Foster. Meanwhile, Foreman retained the title with a close and controversial decision against German fighter Axel Schulz.

Because of the controversial nature of the Foreman-Schulz bout, the IBF ordered Foreman to travel to Germany for a rematch, but Foreman refused, choosing to leave the IBF belt vacant instead. South African Francois Botha travelled to Germany instead and beat Schulz with another close decision to claim the title, but he was stripped of it when he tested positive for illegal substances shortly after.

Third heavyweight title reign

Moorer was then given the opportunity to fight Schulz for the vacant crown in Berlin. On June 22, 1996, Moorer won the IBF heavyweight crown once again, beating Schulz by a 12-round split decision.

He became a three-time heavyweight champion; WBO (1992), WBA/IBF (1994) and IBF (1996–1997). When Moorer held the WBO heavyweight title, it wasn't considered an authentic heavyweight title. Ironically, Moorer has always been recognized as a former light heavyweight champion despite only ever holding the WBO title at that weight.

Moorer's first defense came against Botha on November 9, 1996. In a brutal one-sided bout, Moorer, leading on the cards going into the 12th, ended with a flourish, knocking Botha out 18 seconds into the final round.

In March 1997, Moorer retained his belt with a 12-round decision over previously undefeated Vaughn Bean before parting ways with trainer Teddy Atlas, with whom he'd been experiencing increasing tension since the beginning of their professional relationship. He replaced him with Freddie Roach.

Comeback

After this, he retired from boxing for three years before returning with a knockout of journeyman Lorenzo Boyd. Moorer had begun drinking heavily and weighed 270 pounds. During his comeback, he won three more fights, then seemingly retired again when he was knocked out only 30 seconds into round one by David Tua on August 17, 2002. However, he returned to the ring once again on March 29, 2003, beating Otis Tisdale on points over ten rounds. On August 23, 2003, he beat Brazil's Rodolfo Lobo by knockout in only 64 seconds.

After a layoff of almost a year, he returned on July 3, 2004, losing a ten-round unanimous decision to Eliseo Castillo in Miami, Florida. In December of that year, Moorer rallied from a severe deficit on the scorecards to hand former cruiserweight champion Vassiliy Jirov his first knockout loss. He continued fighting, winning all of his bouts against limited opposition. His last fight was a KO win over Shelby Gross in 2008. Following the fight, Moorer retired from professional boxing.