De La Hoya has defeated 17 world champions and has won 10 world titles in six different weight classes. He has also generated more money than any other boxer in the history of the sport, an estimated $696 million pay-per-view income.

De La Hoya's amateur career included 223 wins, 163 by knockout, with only six losses. He won the United States' only boxing gold medal at the 1992 Summer Olympics, a win which he dedicated to his deceased mother. De La Hoya founded Golden Boy Promotions, a combat sport promotional firm. He is the first American of Hispanic descent to own a national boxing promotional firm and one of the few boxers to take on promotional responsibilities while still active.

On 23 November 1992, De La Hoya made his professional debut by scoring a first round TKO victory. In his twelfth professional fight, he won his first world title at age 20, stopping Jimmy Bredahl (16-0) in the tenth round to win the WBO junior lightweight title. He defended the title once, stopping Giorgio Campanella (20-0) in three rounds.

On 29 July 1994, he knocked out Jorge Páez (53-6-4) in the second round to win the WBO lightweight title. In his first title defense, he defeated John-John Molina (36-3), who had recently vacated his IBF junior lightweight title, by unanimous decision. On 6 May 1995, De La Hoya defeated IBF lightweight champion Rafael Ruelas (43-1-0) in a unification bout. De La Hoya knocked Ruelas down down twice before the fight was stopped in the second round. The IBF then ordered De La Hoya to defend against Miguel Julio. He relinquished the IBF title, and defended the WBO title against undefeated Genaro Hernandez (32-0-1), who relinquished the WBA junior lightweight title to fight De La Hoya. Hernandez quit after six rounds because of a broken nose. In his sixth and final defense of the WBO lightweight title, he knocked out Jesse James Leija (30-1-2) in two rounds.

On 7 June 1996, Oscar De La Hoya fought Mexican legend Julio César Chávez (96-1-1) for the WBC super lightweight championship. De la Hoya, with a record of 21-0 with 19 KOs, defeated Chavez by a fourth round TKO. The fight was stopped due to a bad cut suffered by Chavez. De La Hoya successfully defended his title with a twelve round unanimous decision against undefeated former WBC lightweight champion and number one super lightweight contender Miguel Ángel González (41-0-0).

On 12 March 1997, De La Hoya fought the man many regarded as the best pound for pound fighter in the world, Pernell Whitaker (40-1-1). De La Hoya believed he would knock out Whitaker, saying, "No African-American can take a punch." However, the fight proved to be a difficult one. De La Hoya won by a controversial twelve round unanimous decision to win the WBC welterweight championship.

On 13 September 1997, he defeated Héctor Camacho (63-3-1) by unanimous decision. On 8 September 8 1998, he fought a rematch with Julio César Chávez (100-2-2) and defeated him by eighth round TKO. In his next bout, he faced undefeated former WBA welterweight champion Ike Quartey (34-0-1) and won by split decision. He then defeated Oba Carr (48-2-1) by eleventh round TKO.

After seven defenses of his WBC welterweight title, De La Hoya fought rival and IBF champion Félix Trinidad (35-0) on 18 September 1999, in one of the biggest pay-per-view events in history, setting a record for a non-heavyweight fight. Trinidad was ultimately awarded a majority decision. The judges scorecards came under question after the decision. Fans and boxing analysts called for a rematch, which never happened.

On 26 February 2000, De La Hoya knocked out Derrell Coley (34-1-2) in a WBC title eliminator. After Trinidad moved up to junior middleweight, the WBC awarded De La Hoya the welterweight title, which he lost to Shane Mosley (34-0) by a split decision on 17 June 2000.

De La Hoya took promoter Bob Arum to court in the fall of 2000, trying to break his contract with the promoter. The courts ruled in favor of the Golden Boy in February 2001. Tempers flared during the battle and reached a low in March 2001, when De La Hoya called Arum racist in a newspaper interview, and then apologized for the remarks.