Mayweather, who turns 37 on Monday, revealed the news via Twitter, ending months of speculation about his next opponent.
It had been thought that Amir Khan would get the lucrative fight with pound-for-pound king Mayweather after the Briton signed a deal to fight earlier this year. But confirmation of the bout stalled continuously before Mayweather published a poll on his website asking fans whether they want to see him go up against Khan or Maidana.
Mayweather defeated Saul Canelo Alvarez in his most recent bout in September and subsequently announced the May 3 fight without identifying his next opponent. The site for the match-up has yet to be announced.
Mayweather has a perfect 45-0 record while Maidana is coming off an impressive win against Mayweather's stablemate Adrien Broner which moved him to 35-3.
"Marcos Maidana's last performance immediately brought him to my attention," Mayweather said.
"He is an extremely skilled fighter who brings knockout danger to the ring. I think this is a great fight for me and he deserves the opportunity to see if he can do what 45 others have tried to do before him: beat me."
Maidana added: "I am extremely happy to be facing Floyd Mayweather because it will give me the opportunity to show the world that I am the best welterweight in the division. I just handed a great defensive fighter his first loss and I plan to do the same to Mayweather. I don't care whether he's the best and undefeated. I will bring some real Latino power to him on May 3rd."
Golden Boy Promotions CEO Richard Schaefer told Sports Illustrated that he had some sympathy for Khan who has missed out on what would have been the biggest pay-day of his career.
"He's obviously very disappointed," Schaefer admitted.
"He was going for the big fish, he had him on the hook and then somehow he jumps off. It looked for a while that Amir was going to get the fight. That doesn't mean Amir is out of the race forever. There are a lot of big names at 140 or 147. It's not like it's the end of everything. It's a little detour."