The 27-year-old Joe Smith ended proceedings with a series of blows that included one of his punishing right hands.
In Saturday's fight that Hopkins vowed would be his last the 27-year-old Smith -- who wasn't born when Hopkins launched his career in 1988 -- ended proceedings with a series of blows that included one of his punishing right hands.
Hopkins, who sagged against the ropes and then through them as Smith landed a final left, fell backwards, hitting his head and twisting an ankle.
When Hopkins was unable to make it back into the ring within the mandatory 20 seconds referee Jack Reiss called a halt, making it a technical knockout for Smith at 53 seconds of the eighth round.
"The fighter got hit with a legal punch, went out of the ring and was injured. It's over," Reiss said.
The result was booed by some of the 6,513 at the Forum in Los Angeles, and Hopkins insisted he was pushed, not punched out of the ring.
"I'm really still in shock," said Hopkins, whose resume includes some of the biggest names of his generation and an astonishing 20 straight middleweight title defenses beginning in 1994.
Hopkins became the oldest boxer in history to win a major title when defeated Tavoris Cloud in 2013. In 2014 he beat Beibut Shumenov by split decision to become the oldest to unify world titles.
After a two-year layoff, Hopkins looked all of his 51 years in the early going, but he said he believed he was on his way to turning the tide.
"I know if I hadn't made a mess and gotten knocked out of the ring, I would've come back like I'm known for and would've had my chin," Hopkins said after the result saw his record slip to 55-8-2 with 32 knockouts.
"I had seen him fall, and I kept hitting him until I saw him go out, and I landed that left hook to finish the job," Smith said. "I hit him with four or five clean shots and they were good shots on the button."
Although it wasn't the ending he wanted, "The Executioner" said he wouldn't change his mind about retiring for good.
"I promised I wouldn't," he said of returning. "You come to that point in life where it is final and I'm happy with my life in retirement.
"I belive that the crowd and the fans know for a fact I went out as a soldier, fighting the toughest, baddest opponents.
"Joe was a tough, heavy-hitting fighter," Hopkins added of his hand-picked opponent, who improved to 23-1 with 19 knockouts.
The sometime construction worker from New York said he knew it wasn't the result many came to see.
"I came here to do my job," Smith said. "This is my coming out party, too. I had to finish him."