Padilla turned pro in 1985 and retired shortly thereafter in 1986 after a TKO loss to Dwayne Prim.
In 1991, he returned to boxing and went on a nine-fight winning streak, which included victories over future champion James Page and former champion Roger Mayweather, before challenging for a world title.
In 1993, he captured the WBO Light Welterweight Title in an upset unanimous decision victory over undefeated Carlos Gonzalez.
Padilla successfully defended his title four times with victories over Efrem Calamati (35-0-1), Ray Oliveira, Harold Miller, and former champion Juan Laporte.
During a sparring session with Shane Mosley, Padilla was hit with a hard punch which aggravated a head injury from his last fight.