Meanwhile Italian Francesco Molinari is nearly guaranteed to win the Race to Dubai title after Tommy Fleetwood, the only man who could catch him in the quest to be Europe's No. 1 at the season-ending event, dropped down the field with a 2-over par 74.
Willett then took advantage of the par-five seventh to turn at 17-under, five shots clear of Reed - who had also bogeyed the eighth - and three ahead of Wallace, who made a gain on the ninth after chipping in for par on the eighth.
He birdied the 15th too but a reignited Reed was now the main challenger as he birdied the same hole and went close to levelling up by almost finding birdie at the 16th.
It was the 31-year-old Englishman's first victory since the 2016 Masters, secured with a final-round 4-under-par 68 for an 18-under total of 270.
But that was the last moment of danger for Willett, who managed to recover, making the green in three to two-putt for par and the title. "I know I keep saying everything has been incredible, but if I think where I was before Wentworth this year, if someone told me I would go on to win Wentworth, win on the PGA Tour, win the Open, five points at the Ryder Cup, I probably would have laughed".
"It's been a lot of hard work", said an emotional Willett. It's just nice to be back. "I know how talented Tommy is, and I knew he could do anything today or yesterday".
Reed's birdie on the 18th meant he finished in a tie for second on -16 with Wallace, whose final round 68 capped an excellent week.
After becoming the first Italian to win a major at The Open in July and the first European of any hue to win five points out of five at a Ryder Cup, the popular 36-year-old will enjoy one final momentous occasion. "I'm going to have time to sit down and relax and really think back about the last few months".
"It's more than I ever dreamed of achieving", he said of his 2018, which also included a win on the PGA Tour at the Quicken Loans.
"It's just an incredible achievement again". The way I played, unfortunately it wasn't really in my hands any more.
"It was challenging this week because obviously you try not to, but you are always keeping an eye on what Tommy is doing and I did it very well the first day. I feel the adrenaline might have gone now", Fleetwood said after his round of 74.
The 36-year-old then became the first European player to compile a flawless 5-0 record in the Ryder Cup victory at Le Golf National, having already teamed up with Tommy Fleetwood to make history as the first European pair to win all four of their matches together.