Juan Manuel Marquez is out to inflict the first defeat of Timothy Bradley's career when he challenges for the American's WBO welterweight title in Las Vegas on Saturday.
Marquez, 40, is also bidding to become the first Mexican to win world titles in five weight classes.
Marquez and Bradley beat Filipino great Manny Pacquiao in 2012.
On the undercard, Orlando Cruz will attempt to become the first openly gay boxer to win a world title.
The Puerto Rican fights Mexico's Orlando Salido for the vacant WBO featherweight title.
Two-time Olympic champion Vasyl Lomachenko makes his professional debut at the Thomas & Mack Center and could challenge the winner of Cruz-Salido in his second fight.
The winner of Marquez-Bradley could face another match with Pacquiao, who fights American Brandon Rios in Macau on 24 November.
Bradley, 30, beat Pacquiao on a controversial split decision in June 2012 before Marquez knocked out his arch rival in December.
"Everyone asks me, 'how do you feel at 40 years old?'" said Marquez, who has 55 wins (40 KOs), six defeats and one draw as a professional.
"I feel very happy and I feel great, like a young fighter with a warrior heart."
Bradley boasts a record of 30(12)-0 and is coming off a punishing victory over Ruslan Provodnikov in March.
He absorbed a stream of punishment from his Russian opponent in the early rounds and was almost knocked in the 12th.
Cruz, 32, became the first active boxer to publicly reveal he is gay last October.
He will wear rainbow-coloured trunks in his fight against Salido to signal his support for the lesbian, gay, bisexual, and transgender movement.
Ukraine's Lomachenko, 25, wanted to challenge for a world title in his first pro fight but veteran promoter Bob Arum is confident he will fight for one in his second.
"If everything works out the way we hope, this kid will be the hottest thing in all of boxing," said Arum.
"I've seen some things I've never seen in my life. He could revolutionise the way things are done."
Lomachenko's first official paid fight is a 10-rounder against respected Mexican featherweight Jose Luis Ramirez, who has 24 wins, two defeats and two draws from 28 encounters.
"I want to make history," said Lomachenko, who claims an amateur record of 396 wins and one defeat.
"I don't want to be just a regular great fighter. I want to be the best."