The 38-year-old Morrison, who claims he has no trace of the AIDS virus after taking several HIV tests, dropped Castle with a left hook to the head midway through the second of the scheduled four-round fight at Mountaineer Racetrack and Gaming Resort, about 60 miles northwest of Pittsburgh.
The bearded Castle slowly got up and referee Dave Johnson counted to eight before stopping the match.
Morrison (47-3-1), who that point had landed few punches, fell to his knees afterward and raised his arms skyward.
"I'm satisfied with my performance. I still have a lot of improving to do," Morrison said. "For the first fight in 11 years, with a win under my belt, I'm pretty happy.
"As time goes on, as I spend more time in the gym, I'm going to improve in every area."
Castle hadn't fought in nearly two years but said he wasn't going to fight Morrison until he personally reviewed Morrison's medical records. He got the chance to do so about four hours before the fight.
Castle, wearing black trunks, showed up in the ring 11 minutes before Morrison, wearing red trunks with yellow stars and his nickname Duke, received a solid ovation from the crowd.
Morrison was clearly outpointed in the first round, taking two solid punches to the head.
"I was a little apprehensive, a little jittery, which I think is to be expected," said Morrison, sporting a bruise under his right eye. "I think I got a little lazy with a couple of right hands but I think I was able to come back from it. It knocked me off balance, but I wasn't in trouble. But hey, it was my first fight in 11 years. My defense is going to improve as time goes on."
Morrison said he has been improving on his right hand coordination, "but when you're between a rock and a hard place, you go back to what works."
That came late in the second round, and Castle said he never saw the left hook that ended the match.
"With a guy who was 4-2, I should never have gotten to (fight) him at all," Castle said.
Morrison won the WBO title in 1993 by outpointing George Foreman. He lost it later that year. Morrison, who was featured in the movie "Rocky V," also served a couple of years in an Arkansas prison on drug and weapons charges.
"Tough times never last, but tough people do," Morrison said.
In February 1996, Morrison tested HIV positive just before a scheduled fight against Stormy Weathers. At the time, Morrison said he likely contracted the disease through a promiscuous sex life.
Morrison said earlier this week he has taken several HIV tests while preparing for his comeback and all have been negative.
West Virginia Athletic commissioner Steve Allred approved Morrison's participation after reviewing medical records and consulting with the Association of Boxing Commissions' medical review committee.
Morrison, who didn't address the tests after the fight, said he plans two more bouts in March.
"When the timing comes back, everything else sharpens up as well," Morrison said.