Despite a near disaster at the last, Willett managed to brilliantly save par and a round of 68 and win by two shots with an 18-under par total.
Fellow and reigning Masters champion, Patrick Reed (70) and England's Matt Wallace (68) shared second on 16-under par.
The win is Willett's second victory in Dubai after claiming the 2016 Omega Dubai Desert Classic but a first since April that same year when he superbly won the Masters.
Though there was an anxious moment for the 31-year-old when his drive on the 18th of the Earth Course came to rest inside the marking of a hazard that splits the final fairway but stopping just short of dropping into the water.
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Willett then brilliantly got the ball back onto the fairway to eventually save par and secure the near £1.1m first prize cheque and also the sixth European Tour victory of his career.
'I'm massively proud of myself,' he said.
'It's been a lot of hard work. It's been tough [the past two years].'
Willett won his first major at Augusta two years ago but slipped from a career-high of ninth in the rankings to No. 462 in the world in May this year when he missed the cut in the BMW PGA Championship, and this due to back injury and a loss of form.
He shared the lead with Reed going into the final round, but went three shots clear with an eagle on the par-five second and then made birdie on the seventh.
The father of two young boys then lost that lead after bogeying the 10th and 12th holes, but superbly regained the victory initiative with birdies at 14, 15 and the 17th before holding his nerve on the 18th.
'You never quite know when a win is around the corner. With everything that's happened you're never sure if another win is going to come,' Willett said.
'It's been a hell of a lot of work. It's just nice to be back.
'I've started pretty slowly on the first four or five holes all week – but I got off to a quick one today. For that to happen on a Sunday in the position I was in, I knew I was in a good place.'
Italy's Francesco Molinari is the new European Tour No. 1 despite posting a last day 71 for a six-under par tally and a share of 21st place.
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Molinari also claimed the Race to Dubai title after Tommy Fleetwood failed to win the event.
Molinari has enjoyed a remarkable season, winning his maiden Major at The Open along with his first Rolex Series title at the BMW PGA Championship.
Fleetwood, who needed to win at the Jumeirah Golf Estates to overtake Molinari on the European Tour's money list, finished with a final-round four-under 68 to end 10-under overall, eight shots behind Willett.
'It's incredible,' Molinari said. 'Now I'm going to have time to sit down and relax and really think back about the last few months.
'This morning on the first tee the announcement is the winner of The Open Championship, Race to Dubai leader, it doesn't sound real at the moment.
'It's more than I ever dreamed of achieving. I've seen guys that I think are better players than me not winning Majors and not winning Order of Merits or Race to Dubais. To achieve those things in one single season is just incredible.'
Molinari was also part of Team Europe's Ryder Cup victory over the US at Le Golf National in September, becoming the first European to win five points out of five. Four of those were won in a pairing with Fleetwood.
'It's tough in a way because it would have been probably easier to play against anyone else but him,' Molinari added.
'I know how talented he is and I really thought at some point he was going to win it and put me in a tough spot.
'He's obviously a great guy and a super talented player and I'm sure being younger than me, he's going to win a few more Race to Dubais.'