Mayweather, 45, kept his unbeaten record intact with a unanimous points win against Mosley – but was rocked to his boots in the second round.
The judges scored it 119–109, 119–109 and 118–108 to Mayweather on an impressive night against his fellow American.
But it was far from plain sailing.
The former five-weight world champion – nicknamed ‘Money’ – came through the scariest round of his now 50-0 career before going on to win every round in two of the judges’ eyes to win the lineal welterweight championship.
Mosley made a strong start to the fight after he went to the body early in the first round.
And in the second round the 50-year-old looked to again be getting the better of his opponent after a right hand sent Mayweather stumbling backwards on seriously unsteady legs.
Mayweather, barely standing, made the wise decision to grab hold of Mosley, who desperately tried to break free from his grasp.
His trainer and uncle Roger Mayweather told his charge to go back to the basics after almost a year out of the ring.
Mayweather dominated the rest of the fight afterwards, using his ridiculously-fast hand speed effectively to frustrate Mosley while evading punches.
After the fight Mayweather said: “I came here tonight to give the fans what they wanted to see: a toe-to-toe battle.
“It wasn’t the same style, but I wanted to be aggressive and I knew I could do it.
WATCH: Floyd Mayweather nearly got KO’d before winning every round against Shane Mosley
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“It’s a contact sport and you’re going to get hit. But when you get hit, you suck it up and keep on fighting. That’s what I did.
“I’m happy we finally had a chance to fight. This is a fight the fans have been looking forward to for a long time, and they deserve it.”
And despite having some early moments of success Mosley admitted that he knew that the fight was running away from him after seeing Mayweather make his way back to his corner on shaky legs.
The California native added: “I caught him with my big right hand and I tried to move around but by that time he was too quick and I was too tight.
“After the right hand I thought I needed to knock him out and I needed to do it sooner rather than later.
“But I couldn’t adjust and he did.”