Former Masters champion Reed stayed patient through a frustrating front nine at Chapultepec Golf Club, and as a string of leaders fell away powered to the victory with an 18-under par total of 266.
Birdies at the 15th, 16th and 17th pushed him to 19-under for the tournament, giving him a two-stroke lead.
The cushion proved enough after he pushed his tee shot at 18 well right but limited the damage to a bogey for the narrow win.
“It’s very rewarding,” said Reed, whose only other WGC title came in the same event in 2014, when it was played at Doral in Florida.
“To come back and win my second World Golf Championship — especially with how I had to finish on basically 15 onwards. The last hole was ugly, but it was what I needed to get the job done.”
DeChambeau looked in control after five birdies in a six-hole stretch, his 14-footer at 14 putting him atop the leaderboard at 18-under.
But a three-putt bogey at the par-three 17th proved too much to overcome as he settled for a six-under par 65 and a 17-under total of 267. Justin Thomas, who took a one-shot lead into the final round, faded early on the way to a two-over par 73 that left him tied for sixth. Spain’s Jon Rahm, who could have become number one in the world with a victory, briefly seized a share of the lead thanks to birdies at four of his first five holes. But two birdies and two bogeys coming in weren’t enough for the Spaniard, who shared third on 269 with South Africa’s Erik van Rooyen, one stroke in front of world number one Rory McIlroy.
“It definitely tested me today,” Reed said. “The birdie barrages that were happening, it seemed like I was having to get up and down at every hole on the front nine. I think I only hit three greens on the front nine.” He began to gain ground with a tap-in birdie at the 12th, and made another from less than three feet at 15. Another short birdie at 16 was followed by a tough 17-footer at the 17th.
Reed’s perseverence will pay off with a rise to eighth in the world.
The satisfying victory capped a week in which Reed again found himself criticized — this time by compatriot Brooks Koepka — for an incident at the Hero World Challenge in December when video showed him moving sand behind his ball in a waste area.
He accepted a two-stroke penalty and although he denied intentionally trying to improve his lie Reed hasn’t been dogged by the affair all year.
Leading final round scores
266 - Patrick Reed 69-63-67-67
267 - Bryson DeChambeau 68-63-71-65
269 - Jon Rahm (ESP) 72-69-61-67, Erik van Rooyen (RSA) 70-62-67-70
270 - Rory McIlroy (NIR) 65-69-68-68
271 - Hideki Matsuyama (JPN) 69-64-71-67, Tyrrell Hatton (ENG) 69-68-66-68, Justin Thomas 67-66-65-73
272 - Billy Horschel 68-71-68-65, Kevin Na 71-68-65-68
273 - Paul Casey (ENG) 69-68-66-70
275 - Abraham Ancer (MEX) 70-70-67-68, Gary Woodland 70-69-65-71
276 - Xander Schauffele 72-72-66-66, Sebastian Munoz (COL) 71-66-72-67
277 - Carlos Ortiz (MEX) 75-68-66-68, Rafa Cabrera Bello (ESP) 71-71-67-68
278 - Bubba Watson 67-72-71-68, Tommy Fleetwood (ENG) 70-69-70-69, Kevin Kisner 73-69-67-69, Benjamin Hebert (FRA) 73-70-65-70
279 - Brandt Snedeker 76-69-70-64, Lee Westwood (ENG) 69-70-70-70, Cameron Smith (AUS) 73-73-69-64, Matt Kuchar 75-67-67-70
280 - Adam Scott (AUS) 74-68-68-70, Zander Lombard (RSA) 73-68-69-70, Scottie Scheffler 73-70-67-70