The Englishman was eight shots behind Dustin Johnson – who was six clear at the top of the leaderboard – when he teed off, and remained six behind at the turn after playing his first nine holes at Sheshan International Golf Club in level par.
Rose then produced five birdies in a stunning back nine of 31 to get to 14-under after a 67, with Johnson slumping to a closing 77.
The World No 1 finished in a tie for second at 12-under alongside Swede Henrik Stenson and reigning US Open champion Brooks Koepka.
The victory is Rose’s second World Golf Championships title after the 2012 WGC-Cadillac Championship, which started his run of six consecutive seasons with a European Tour victory – the longest active streak on Tour – and moves him up to third in the Race to Dubai Rankings presented by Rolex.
‘This is really, really satisfying,’ he said. ‘All players pride themselves on winning and I’ve won every year since 2010 (worldwide). I was very aware that that was slipping away from me this year.
‘To win a WGC is just amazing, they count for so much on both tours. It’s an incredible start to my 2018 PGA Tour campaign and gives me a real shot in the Race to Dubai as well.’
Any thoughts of a procession for Johnson were quickly forgotten as the World No 1 got in bunker trouble to drop a shot on the first and then lost his ball off the second tee for a bogey-bogey start.
Rose took advantage of the par-five second, and when he holed a lengthy double-breaker over the ridge on the third, he was alongside Koepka four shots back.
Koepka three-putted the third and also bogeyed the fourth after finding sand, with Rose dropping a shot on the sixth thanks to bunker trouble of his own.
Stenson had started the day with five pars, but a brilliant tee-shot into the sixth moved him to 11-under, and he was soon joined by Rose who got up and down from a bunker on the short seventh.
Stenson did not attempt to drive the par-four and set himself up for a smart approach that cut the lead to three shots.
Koepka left himself a flick-in to the same hole to get back to ten-under, but Rose three-putted the eighth and then found the hazard on the ninth to drop back.
He bounced back with a birdie on the 11th, but the momentum was now with Koepka, who holed a lengthy putt on the tenth and a six-footer on the 11th.
Stenson dropped a shot on the same hole after getting a plugged lie, but a brilliant tee-shot on the 12th saw him recover it, with Johnson making a third bogey of the day.
All eyes were on the final group, but ahead of them Rose birdied the 13th and then took advantage of the par-five 14th to move within striking distance.
Koepka also capitalised on the 14th to cut the lead to one, but the drama was to come on the next as both Koepka and Johnson got plugged in bunkers. Both men failed to get up and down, but Koepka made a double-bogey after three-putting from the fringe, and all of a sudden the event was wide open.
Ahead on the 16th, Rose played a stunning bunker shot to share the lead, and he briefly held it on his own after Johnson hit a poor tee-shot and found sand with his second for another bogey on the same hole.
Stenson bogeyed the penultimate hole and Koepka was the only one of the leading contenders to birdie the last for a 71, with Stenson recording a 70 and finishing second at this event for the second consecutive season.
‘I needed to regroup going into the back nine,’ added Rose. ‘I kind of told myself I was four down playing the golf course. I played match play against the golf course coming in.
‘I didn’t know if 13 [under] was going to be good enough, I kind of figured I was playing for second and I thought 13 was going to be an important number to get to for that.
‘I saw DJ get back to about 14 or 15 and the game was on, so it was certainly exciting coming down the stretch.’
Spaniard Rafa Cabrera Bello and Americans Peter Uihlein and Kyle Stanley finished at eight-under, a shot clear of Brian Harman and two ahead of England’s Matthew Fitzpatrick and Austrian Bernd Wiesberger.
Saffa results: