Two and a half years after undergoing surgery to remove a brain tumor, Woodland soaked in a special five-shot victory after closing with a cruisy three-under-par 67 at Memorial Golf Club.
Never threatened, the American reached 21 under for the championship to comfortably hold off Dane Nicolai Hojgaard, who could only manage a Sunday one-over 71.
Defending champion Min Woo Lee (67) tied for third, six shots behind Woodland, with fast-finishing American Johnny Keefer (64), while Sam Stevens (68) was outright fifth at 14 under.
In a welcome confidence booster two weeks out from the Masters, Lee's fellow Australian Jason Day (68) was joint sixth at 13 under.
But the spoils, including the $US1.78 million winner's cheque and a ticket to the Masters, belonged to Woodland, the 41-year-old 2019 US Open champion who added a most improbable fifth PGA Tour title to his CV with his first victory in almost seven years.
After doctors removed a tumor that was pushing on the part of his brain controlling fear and anxiety, Woodland revealed recently he still suffered from severe PTSD, including panic attacks and fear.
Asked what he was most proud of after completing what seemed unimaginable two years ago, Woodland said "that I didn't give up" while choking back tears.
"You know, golf's like a lot like life. It's not easy, you hit bad shots and you hit bumps in the road in life. You just got to keep fighting and I'm proud that I did that.
"Anyone that's struggling with something, I hope they see me and don't give up - just keep fighting."
Joint runner-up last year with world No.1 Scottie Scheffler behind Lee, Woodland credited the entire golfing community for supporting him through his life-threatening ordeal.
"I haven't felt like this in a long time," he said.
"I kept telling myself I've been here before and I've done it, but I tried to slow down a little bit today and take it in because this a couple of years ago didn't seem like it was possible.
"I took in the love and support of everyone and I just kept telling myself I wasn't alone."
Australian Karl Vilips (67) also posted a top-20 finish, sharing 19th spot at nine under, one stroke ahead of former world No.1 Adam Scott, who aced the par-3 11th hole in a closing 71.
Scott struck a beautiful eight iron for his fourth PGA Tour hole in one, having also jagged two aces at Pebble Beach and one at Augusta National's famous 16th.
"It was a fun moment on what was a pretty ordinary day to that point," Scott said.
Scott was equally as elated for Woodland.
"I'm just so pleased for Gary playing so well," he said.
"I just really look up to him as a mate who put it out there just a couple weeks ago on television, what he's dealing with. It is inspirational.
"But him being on the course, like he said, and we're around him a lot in the physio room and the locker room. I think it does help him being out here."
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