Moorer is a native of the Pittsburgh suburb of Monessen, PA, but for most of his career, he trained under the tutelage of hall of fame trainer Emanuel Steward in Detroit. As a member of Steward's Kronk Gym team, he was teamed up with such boxers as Thomas Hearns and Gerald McClellan.

Moorer had a fast but steady rise through the professional boxing ranks. He debuted on March 4, 1988, knocking out Adrian Riggs in the first round. He spent the year taking on a rather ambitious fight schedule, in terms of quantity if nothing else. 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 world 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 world champion Leslie Steward, 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.

1991 saw Moorer commence his campaign at the Heavyweight division. He rolled through the competition en route to securing an opportunity to fight for the vacant WBO world Heavyweight championship the following year. He knocked out former Evander Holyfield challenger Bert Cooper in the fifth round, making him only the second man to go directly from holding a world light heavyweight title to holding a heavyweight title. That night, he also became the first left-handed boxer in history to become a world heavyweight champion.

He did not defend the WBO heavyweight belt. Moorer and 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 10 round decision over Mike Evans. Moorer then landed a title shot, and challenged Evander Holyfield for the IBF and WBA title belts. Holyfield was considered the true, lineal champion at the time. On April 22, 1994, before a Pay Per View audience, Moorer overcame a second round knockdown and went on to win a majority decision over Holyfield.

In his first defense of those belts, on November 10, 1994, Moorer was ahead on all three judges' scorecards when he received a right hand to the chin by George Foreman in round 10, getting knocked out and losing the world championship. In addition to the belts, he also lost his undefeated record that night.

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 Axel Schulz. Because of the controversial nature of the Foreman-Schultz 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 Schultz with another close decision to claim the title, but he was stripped of it when he tested positive for illegal substances shortly after.

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

His first defense, against former world champion Botha, came on November 9, 1996. It was, according to Ring Magazine, one of the fights of the year. In a brutal give and take war, Moorer was leading on two of the three scorecards going into the 12th and final round, then ended with a flourish, knocking Botha out with just 18 seconds left in the bout.

In March of 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 an increasing amount of tension since the beginning of their professional relationship. He replaced him with trainer Freddie Roach. On November 8 of that year, Moorer visited the canvas five times in his rematch with Evander Holyfield before ringside doctor Flip Homansky advised referee Mitch Halpern to stop the bout in round eight.

After this, he retired from boxing for three years before returning with a knockout of journeyman Lorenzo Boyd. 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 journeyman Otis Tisdale on points over 10 rounds. On August 23, 2003, he beat Brazil's Rodolfo Lobo by knockout in only 64 seconds.

After a layoff of almost one 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 world Cruiserweight champion Vassily Jirov his first knockout loss. The victory revitalized his career and placed him back amongst the ranks of contention for the world title. Following the fight Moorer decided to be a trainer and retire from boxing.

Moorer scored knockouts in each of his first 26 bouts, placing him in the exclusive list of boxers who have won at least 20 fights in a row by knockout, alongside such other fighters as Foreman, Wilfredo Gomez, Carlos Zarate, John Mugabi, Khaosai Galaxy and Aaron Pryor.

As of April 2005, his professional ring record stands at 47 wins, 4 losses and 1 draw, with 37 wins by way of knockout.