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Mayweather, who was defending his title for the first time since serving close to three months in jail last year after being convicted of domestic violence, dominated Guerrero for the majority of the fight at the MGM Grand Hotel and Casino.
All three judges scored the 12-round fight 117-111 in favour of Mayweather.
In his first fight in a year, the 36 year old Mayweather also snapped Guerrero's 15-fight win streak dating back to 2005.
While Mayweather improved to 44-0 with 26 knockouts, Guerrero fell to 31-2-1 with 18 wins inside the distance.