Mosley (left) was ahead on two of the judges' cards after 11 rounds
Shane Mosley unleashed a devastating left hook to knock out Ricardo Mayorga with one second left in their non-title light-middleweight bout in California.
The 37-year-old Mosley floored Mayorga twice in a final round, claiming the KO with a flurry of punches in a temporary outdoor ring at the Home Depot Center.
American Mosley had been ahead on two of the judges' cards after 11 rounds.
Saturday's knockout was the 38th of his career and could force the 35-year-old Mayorga to consider retirement.
"I closed the show," said Mosley, a four-time world champion who has now won 45 of his 51 fights. "I got the knockout."
Nicaraguan Mayorga, himself a three-time former world champion, pressed the attack in the first three rounds before Mosley took over.
The turning point came in the sixth when Mosley landed several solid rights that hurt the unorthodox Mayorga, who had a 10-pound weight advantage.
I will tell you one thing - he hit harder than I thought he would
"I could feel him getting weaker," said Mosley. "He was trying to play like he was strong. He might have stole some rounds here and there but I wanted to go for the knockout.
"Mayorga is tough. He took some good shots early but I knew I could wear him down. Early on I was trying to figure him out what he was doing. He was throwing crazy punches."
Mayorga, who has now lost four of his last seven fights, added: "I thought I was doing well and I came out to win in the 12th round and he caught me. I will tell you one thing - he hit harder than I thought he would."
Mosley's previous fight was in November of last year, when he lost a 12-round unanimous decision to Miguel Cotto.
He now wants to fight the winner of the rematch between Cotto and WBA welterweight champion Antonio Margarito.
Earlier, undefeated Andre Berto defended his WBC welterweight title with a 12-round unanimous decision over fellow American Steve Forbes.
Berto, 25, outpunched 31-year-old Forbes in the longest fight of his career, winning 118-109, 118-109 and 116-111.
In Hamburg, Panama's Guillermo Jones stopped Firat Arslan of Germany to win the WBA cruiserweight title.
Jones dominated the fight and hurt Arslan with a series of bruising blows to the head, causing the fight to be stopped with 27 seconds left in the 10th.