The Irishman has come close to winning the tournament in the past, on a course he clearly loves, most notably in 2014 when he finished a shot beind Rory McIlroy.
This time the roles were reversed, Lowry getting the better of his close friend as a closing 65 saw him post 17 under and take the win. He did not drop a single shot across the 54 holes, with the tournament played over only three rounds following the death of the Queen and the subsequent cancellation of play on Friday.
Jon Rahm threatened to storm from behind and set a clubhouse target that could not be matched, his Sunday 62 leaving him on 16 under par following an eagle on the 18th to cap off a stunning back nine.
Lowry two-putted on the final green to go a shot better, though McIlroy was waiting behind on the fairway and still had a chance to take it to a play-off with an eagle.
He fired a long iron to just over 20 feet and was millimetres away from draining the putt, the ball instead just hanging on the edge of the hole as an emotional Lowry watched on a TV screen.
Viktor Hovland had a share of the lead going into the final round but had to settle for a tie for fifth three shots back, with defending champion Billy Horschel also in the top ten.
The American voiced his opposition to players from the Saudi-backed LIV Golf series being in the field, with 18 of those involved in the breakway tour teeing it up at Wentworth.
McIlroy was similarly uncomfortable, while Lowry said at the start of the week he found it difficult to stomach some of those who had not previously been regulars on the DP World Tour competing.
It was therefore no surprise that the Irishman was particularly satisfied to come out on top.
“I made no secret how I feel about the whole thing,” Lowry said. “I wanted to win for myself first and foremost, but for everyone that has stayed loyal to this tour. I really feel this is one for the good guys.”
He added: “It means a lot. It’s been a good year, but felt like I’ve been close a few times and only a few tournaments left this season and I really wanted to win one and this was top of the list.
“I’m so happy. I can’t put into words how happy I am, how much I love this tour, this tournament. I’m the happiest man in the world right now.
“I got to 16 and was trying to get past that but had to worry about Rory behind me, he could do anything the last few holes how good he is. I just tried my best to hit shots, I told my coach I need to allow myself to play golf. I’m playing the best golf of my life and I did that.”
McIlroy, who finished a shot back of Lowry alongside Rahm after a final round 67, said: “I’m okay. I think Shane winning softens the blow. If it had been someone else, I might not have felt as comfortable with it as I am. Seeing a friend win is always great and I am really happy for him.”
“I gave myself a look to take it into a play-off and I thought three feet out that it was going in the hole,” he added.
“Overall it’s been another really good week. The consistency and the level of my golf is probably as high as it’s ever been, it feels good.
“It’s been a great year for me. I would have loved to have taken Shane a couple of extra holes, but this is still another great week. I’m leaving here very, very happy”