Stephens struggled throughout in a match that saw just three of the 17 games played won from the end of the court in the full glare of the sunshine, losing 6-2, 6-3.
Stephens was an 83rd-ranked outsider when she roared to the title past year, cementing her return from an 11-month injury absence.
Next match, can employ that strategy against No. 19 Anastasia Sevastova of Latvia.
Sevastova said: "It was an unbelievable journey, this three, four years". When you go to a tournament, it starts all over again. "After I stop at some point I will look at it and I will be proud of myself for sure".
"I hope I will enjoy it, playing semi-finals".
Williams reached her 36th Grand Slam semifinal and her 12th at Flushing Meadows, where she is a six-time champion.
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The racetrack, at Del Mar Fairgrounds, is located about 21 miles north of downtown San Diego along the Pacific coast. The man pulled out a silver plated semi-automatic handgun and fired several shots into a crowded area.
Sevastova is one of the wiliest players on tour, mixing up slices, spins and angles and generally making life very uncomfortable for a player like Stephens who feeds off consistency of pace.
In doubles action, Rohan Bopanna's campaign ended as he and his French partner Edouard Roger-Vasselin lost the quarter-final match 3-6, 4-6 to Colombians Juan Sebastian Cabal and Robert Farah.
Stephens said that despite the manner of her defeat on Tuesday she was content with what she had achieved at this tournament.
The tactic certainly paid off against Stephens, who had to contend with a sinus infection in addition to the sweltering temperatures on Arthur Ashe Stadium. "I'm just able to beat those girls and just to go through somehow". It was just a tough day. "But on the same time, not make too many mistakes", said the 24-year-old Thiem. "But anyway it's a good stat, it's something positive, it's something that shows I've been competitive on all surfaces in practically all the weeks I've played this year, and I'm happy about it".
Sevastova earned her second career title - and first in seven years - at Mallorca in 2017 - finishing at 16th in the world last year after a season that included her US Open last-eight run. The spirit of the game was moving fast in Sevastova's direction as she whipped up a 6-2 first set victory.
Stephens takes the tack that she isn't exactly defending a title.
"It's going to be a close match, I think", she said. Just keep building. There's four more tournaments left.