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US 18th seed Brian Harman never trailed in dispatching McIlroy 5&3 and capturing his group with two wins and a draw.
Spieth was knocked out by US Ryder Cup partner Patrick Reed, who won their much anticipated match 2&1.
Reed, ranked 23rd in the world, never trailed and rolled in a 40-foot putt from off the 17th green to end Spieth’s hopes of a first title of 2018.
Both will now try to regroup with the first major of the year, the Masters, two weeks away.
Sergio Garcia, tuning up for his Masters title defence at Augusta National, rallied from 2 down through 11 holes to beat rising US star Xander Schauffele 3&1 and reach the last 16.
“Xander played unbelievable on the front nine, tricky conditions, and he kept making good putt after good putt on me,” Garcia said. “So I was just hoping to stay in it and give myself some chances as soon as he gave me a little opening on 12.
“And then I was able to make a great birdie on 13, 15 and 16,” added Garcia, who next faces American Kyle Stanley.
Thomas pummelled Italian Francesco Molinari 7&5 to set up a meeting with South Korean Kim Si-woo — a 2 up winner over Webb Simpson.
The only thing Thomas could find to regret was that the match only lasted through 13 holes.
“Today I’d be really excited to see how low I could go,” said Thomas, who will take on Kim in the round of 16. “I could post a serious number.”
– Weary McIlroy –
McIlroy, managed only two birdies in his final competitive tuneup for the Masters, the only major title the Northern Ireland star needs to complete a career Grand Slam.
“Rory did not play his best golf today but I played extremely well,” said Harman, a two-time winner on the US PGA Tour.
“I’m proud of the way I came out. Rory is an intimidating guy. He hits it a mile. I had this one (match) circled this week and I’m glad I came out and performed pretty well,” added Harman, who set up a meeting with two-time Masters winner Bubba Watson.
Watson birdied the last two holes to halve his match with 64th-seeded Julian Suri.
McIlroy, coming off a victory at Bay Hill last Sunday, admitted he was feeling weary.
“That takes it out of you being in contention, and all that mental energy,” he said.
Other top players who didn’t make it past group play included world number one and defending champion Dustin Johnson, former world number one Jason Day, five-time major winner Phil Mickelson and Spain’s Jon Rahm.
South Africa’s Louis Oosthuizen beat Day 2 up, then won his group in a playoff against Jason Dufner with a par at the first hole.
American Charles Howell rolled unbeaten to his group crown by downing Japan’s Satoshi Kodaira 2&1.
That eliminated Mickelson, seeded 18th, who had kept his hopes alive by edging Spain’s Rafa Cabrera Bello 1 up.
Thailand’s 28th-seeded Kiradech Aphibarnrat booked a last-16 clash with Howell with a 4&3 victory over third seed Rahm, who had already been eliminated and finished the week winless.
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