De León, a native of Trujillo Alto, Puerto Rico, first won a world title when he faced the WBC world champion Marvin Camel on November 25, 1980, replacing David Pearce the Great Britain boxer on the undercard of Sugar Ray Leonard and Roberto Durán's second fight in New Orleans.
He defended his title against Yaqui López by a knockout in four at San Jose, California, and with decisions over Anthony Davis and Bashiru Ali.
De León joined the likes of Sugar Ray Robinson and Muhammad Ali in becoming one of the few boxers ever to win one division's world championship at least three times, defeating Benton by decision.
He made a couple of defenses in Italy and then in 1988, he defended the title against Uruguayan José María Flores Burlón in Atlantic City, New Jersey, winning by twelve rounds in a unanimous decision but then he lost his titles in a unification bout with WBA and IBF world champion Evander Holyfield, by technical knockout in the eighth round, also in Las Vegas.
He went to London, where he beat the WBC's number two ranked contender, Sammy Reeson, by a knockout in the ninth round, breaking his own record and was crowned world cruiserweight champion once again.