The undefeated boxer has agreed a bumper six fight deal with Showtime in the USA after spending his career with HBO - which could also put paid to any last hopes of him facing Manny Pacquiao.
Floyd Mayweather to fight Roberto Guerrero after agreeing new TV deal
The boxer, who has agreed a deal to switch his fights from long-standing broadcast HBO to Showtime in the USA, will take on the 29-year-old interim WBC welterweight champion on May 4.
Mayweather, who last fought in May 2012 when he beat Miguel Cotto for the WBA light-middleweight belt, is likely to step back down to welterweight as he looks to extend his record to 43-0.
It will be the first time he has stepped into the ring since being jailed for domestic battery last year.
Guerrero, who boasts a 31-1-1-2 record, retained his interim title in his last fight, defeating Andre Berto by unanimous decision last November.
Earlier this month, unbeaten five-weight world champion Mayweather had hinted he was close to reaching an agreement to fight Devon Alexander, the IBF welterweight title holder, just days after Alexander had withdrawn from a fight with mandatory challenger Kell Brook.
Mayweather called the new TV deal, for up to six fights over 30 months, the biggest in boxing history - but said financial details of the contract were confidential.
Should all six fights take place and his pay-per-view averages of more than one million buys per bout hold steady, Mayweather claimed the deal would be the largest for an individual athlete in sports history.
The switch in broadcasters could finally put paid to any hope of Mayweather facing Manny Pacquiao, who has been affiliated with HBO for many years.
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