By Mark Lamport-Stokes
Mayweather, the 4-1 favorite, has an unblemished 40-0 record as a professional with 25 knockouts but Sugar believes the flamboyant 33-year-old will be undone by the bigger and faster Mosley.
"Not only do I think he can win, and obviously I think he will, but I'm a contrarian," Sugar, 73, told Reuters on the eve of the scheduled 12-round bout at the MGM Grand Garden Arena.
"Not just the one pound on the scale but if you look at the dimensions, particularly in the shoulders and his reach."
Mosley, a world champion in three weight divisions with a career record of 46-5 with 39 knockouts, tipped the scales at 147 pounds on Friday compared to Mayweather's 146.
His reach, at 74 inches, exceeds Mayweather's by two inches.
Both fighters are renowned for their lightning hand and foot speed, along with sublime boxing skills, but Sugar believes Mosley has formulated a winning recipe.
"I think he knows how you can beat Mayweather, and it's not with his right hand," said Sugar, a cigar-chomping member of the International Boxing Hall of Fame.
"That right hand is a looping right hand and it was made for (Antonio) Margarito but it's a kind of punch that you won't hit Mayweather with."
De La Hoya held the upper hand in the early rounds before losing his crown to Mayweather in a split decision.
Mayweather beat Juan Manuel Marquez in his most recent bout in September after a 21-month retirement while Mosley has not fought since a ninth-round upset of Margarito in January 2009.
"I think the rust factor is going to be more telling on Mayweather," added Sugar, author of numerous sports books and a former publisher and editor of Ring Magazine.
"Yes, Mosley is five years older and I don't know how to count it in boxing years.
"But with a great defensive fighter, and there's no question Mayweather is, any rust factor makes him a nano-second slower in his reflexes so that punches that were once this are now that.
"I do see where it could have even that much of an effect that it could be fatal (for Mayweather)."
(Editing by Ian Ransom)