[3] His record of the most wins in unified championship bouts in boxing history, shared with Muhammad Ali, was unbeaten for 40 years.

He was defeated by Tony Perez and Alfredo Urbina, both by decision, but he beat JC Morgan, by knockout in seven rounds, in Venezuela.

He won three more fights in 1965, including another win against Morgan, before seeing a raise in opposition quality when he faced the former world Junior Welterweight champion Eddie Perkins, beating him by decision in ten rounds.

During this period, Nápoles also became a fan favorite in southern California, and, after beating Fate Davis, on February 15, 1969, in Mexico, he was given an opportunity to win the world championship when he faced the then-current champion Curtis Cokes in Inglewood, on April 18.

Nápoles beat Cokes by a knockout in round 13 to become world welterweight champion, and, as was becoming common place for him, he wore a sombrero after the fight.

Nápoles began the 1970s, by defeating Ernie "Indian Red" Lopez by a knockout in round 15 in front of an audience that included former world champion Sugar Ray Robinson on February 14, 1970.

But after winning two non-title bouts, he suffered an upset when he was stopped due to being cut in four rounds by Carmen Basilio's nephew Billy Backus, who took the world's Welterweight title from Nápoles on December 3 at Syracuse.

After three non-title wins, including one over Jean Josselin, he faced Hedgemon Lewis on December 14, retaining the world title with a decision in 15 rounds, but Nápoles' training habits were suffering; he was alleged to be coming into the gym stinking of alcohol with an attitude towards his seconds.

[5] This would be Nápoles' only bout at the middleweight division, as he was defeated by quitting the match, officially losing by a seventh-round technical knockout.