Hopkins scored a unanimous decision to dethrone 31-year-old fellow American Cloud for the International Boxing Federation (IBF) light heavyweight title.
Hopkins was 46 in 2011 when he beat Canada's Jean Pascal to win the World Boxing Council (WBC) light-heavyweight crown.
Hopkins waved his hands, stuck out his tongue, shook his head and smiled.
The veteran boxer relied on his defense and strong right hand on Saturday night along with his usual veteran tactics.
But it was the strong punch that opened up a cut above Cloud's left eye that put Brooklyn's Barclays Center crowd on its feet.
"B-Hop, B-Hop," they chanted.
And six rounds later the crowd was cheering the oldest fighter to ever win a world title as Hopkins won by unanimous decision over Cloud. After the bell, Hopkins leaned over the broadcast table and shouted at middleweight champion Andre Ward.
Hopkins sealed the decision (117-111, 116-112, 116-112) with a strong final three rounds. He used his lateral quickness to avoid most of Cloud's power punches. In the 12th round, Hopkins connected with a thudding uppercut to the stomach that again caused the crowd to cheer his name. With a nearly unblemished face, Hopkins forced the area around both of Cloud's eyes to swell.
In the sixth round, Cloud suffered a cut above his left eye and the fight was paused midway through the round for Cloud to receive medical attention. Cloud pleaded with the referee that it was an elbow from Hopkins that caused the cut. The referee said it was an accidental head butt.
The arena replay showed that it was a punch from Hopkins that opened the cut. Once the crowd saw the replay, they chanted Hopkins' name. With the crowd behind him, Hopkins rallied through the next round. He backed himself into a corner, gestured for Cloud to come closer before meeting his foe with a series of jabs. Hopkins turned out of the corner and away from Cloud's attack, which caused Cloud to fall into the ropes. With Cloud helpless, Hopkins waved his arms and peppered Cloud with a few punches.
After sustaining the cut, Cloud began to fight with a sense of desperation. He attacked Hopkins wildly, seeking the knockout. In the eighth round, his aggressiveness paid off as he caught Hopkins with a right hook to the face.
Hopkins was on the move in the second round as he kept his distance from Cloud's combinations and forced him against the ropes. But Hopkins failed to capitalize and was only able to connect with a short right hand.
Hopkins again effectively used his left hand as a way to make room for his right as he badgered Cloud with soft body shots before connecting with a hook.