The American left-hander went into the final round at a very wet Royal Liverpool Golf Club with a five-shot lead and suffered his only real scare when Masters Champion Jon Rahm closed to within three after just five holes on Sunday afternoon.
Harman rallied, though, firing back-to-back birdies at the sixth and seventh before bouncing back from his third bogey of the day on the 13th with two successive gains on the 14th and 15th to put one hand on the Claret Jug.
And he closed round with three successive pars to sign for a final-round 70 and finish the tournament on 13 under par.
Harman's only other 54-hole lead at a Major had come at the 2017 U.S. Open Championship at Erin Hills, where he began the final day with a narrow one-stroke cushion but finished in a tie for second.
He was not to be denied this time, though, as a world-class chasing pack failed to truly threaten his commanding lead.
World Number Three Rahm, Jason Day, Tom Kim and Sepp Straka finished in a tie for second on seven under, with four-time Major Champion Rory McIlroy and first-round co-leader Emiliano Grillo another shot back.
Harman said: "It’s pretty surreal. It really hasn't sunk in yet. I’m not going to let (the Claret Jug) out of my sight for the time being.
"To win what I consider the greatest prize in golf is as good as it gets.
"I've got to thank my wife and family back home. I sure miss them and can’t wait to get back to them tomorrow.
"First I’m going to have me a couple of pints out of this here trophy, I believe.
"This golf course was a real test. It was set up so great even with the weather, so thanks to everyone that helped put it together.
"I want to thank the R&A for putting together such an incredible Championship. I couldn’t be happier to be its champion."
“A tremendous par”
Harman saw his five-shot overnight advantage extended to six early in the final round as playing partner Cameron Young dropped a shot at the first.
But when the runaway leader pulled his approach at the second into the right rough and failed to get up and down - surrendering his first bogey since the fourth hole on Saturday - the lead was back to five.
The 36-year-old pulled off a tremendous par save at the third before narrowly missing his outside birdie chance on the fourth as he remained five shots in front on 11 under.
But after sending his tee-shot into a bush at the long fifth, Harman took a drop there and was unable to save par, allowing Rahm to close the gap to three strokes after the Spaniard birdied the same hole.
Harman bounced back in style, however, taking advantage of the short sixth thanks to a 14-foot putt, before draining his birdie try from 24 feet on the seventh to restore his five-shot lead.
The American then closed his front nine with pars at the eighth and ninth to head into the turn well and truly in control.
Harman bogeyed the par-three 13th after missing the green but recovered immediately with a 40-foot birdie putt on the 14th to return to 12 under.
He notched another birdie on the par-five 15th courtesy of an eight-foot putt, moving five clear once more in the process.
After safely parring the 16th and 17th to find himself six ahead with one to play, Harman did not take any risks at the last, instead opting to lay up and settle for a third straight par to wrap up a convincing win.
DP World Tour