Undaunted, Arguello began another streak of wins, and found himself in the ring with a world champion again, this time challenging Marcel's successor to the throne, sensational Mexican powerpuncher Ruben Olivares in Los Angeles. After a very compelling bout, Arguello and Olivares landed straight left crosses, but, in a scene comparable to that of Gene Hackman's and Leonardo DiCaprio's shooting scene in The Quick And The Dead, Olivares's left hand caused a visible pain expression on Arguello's face, but Arguello's left hand caused Olivares to crash hard against the canvas. A few seconds later, Arguello was the new Featherweight champion of the world.
Arguello defended this title a few times, then moved up in weight to challenge world Junior Lightweight champion Alfredo Escalera in Bayamon, Puerto Rico. Escalera had been a sensational champion with ten defenses, and he had dethroned Kuniaki Shibata in 2 spectacular rounds in Tokyo. This was expected to be an incredible fight, and it was. In what experts consider one of the most brutal fights in history, Escalera had his eye, mouth and nose busted early, but was rallying back in the scorecards when Arguello finished him, once again in the thirteenth round.
His reign at Junior Lightweight saw him fend off the challenges of Escalera in another sensational rematch held at Rimini, Italy, as well as boxers with names like two-time world champ Bobby Chacon, two-time world champ Rafael 'Bazooka' Limon, Ruben Castillo, and Diego Alcala, taken apart in only one round.
Arguello then moved up in weight again, and this time he had to go to London, England, to challenge less sensational but still awkward and accomplished world champion Jim Watt. Watt gave him a very good fight, but his lack of power and Arguello's technical skills gave Arguello a unanimous 15-round decision, thus making him only the fifth boxer to win titles in 3 world categories, the first one to do it since Henry Armstrong 41 years before, and the first Latin American to do it. He had to face some less dangerous though still hungry challengers in this division, the only exception being the sensational prospect Ray Mancini, a future world champion and subject of a TV movie himself. Mancini and Arguello engaged in one of the most entertaining bouts of the 1980s, with Arguello prevailing after 14 give-and-take rounds.
After defeating James 'Bubba' Busceme by a knockout in 6 rounds, Arguello decided it was time to move again, and on November 12th, 1982, he tried to make history and become the first ever world champion in 4 different categories, meeting the tough and heavier future Hall-of-Famer Aaron Pryor, in what was billed as The Battle of The Champions in Miami, Florida.
It was an extremely brutal and controversial contest, with Arguello being left helpless against the ropes in the 14th round, referee Stanley Christodoulou stepping in to stop the fight. Arguello was hospitalized after the fight, and he took a few months off before getting back into the ring.
It was discovered months after the fight, and with the help of a video tape, that Pryor's corner had gotten a mysterious bottle into the ring and given it to their fighter after the 12th round, during which Pryor was badly shaken by Arguello's punches and looked like he could go at any time. What that bottle contained is anybody's guess, but it became the grounds for the WBA to grant a rematch, which was fought September 10th, 1983. Arguello again gave Pryor all he could handle, but again came up short, this time losing by a knockout in the 10th. He announced his retirement after the rematch.
Arguello later joined the Contras in his native Nicaragua but after a few months in the jungle he retired from the war. He attempted several comebacks during the late 1980s and early 1990s but all these comebacks failed to bring him back his old luster. He has also run into trouble with the law, but now he is trying to get his life back on track.
Arguello's possessions in Nicaragua had been taken by the Sandinista government in 1980 and Arguello had to move to Miami. Because of his public criticism of the Sandinista government, Arguello was admired by many Cuban residents of the area. Still intimidated by Fidel Castro's figure, those Cubans saw Arguello as a person who could publicly talk against Communism for them.
Arguello is now a member of the International Boxing Hall Of Fame.