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He was broken in the last set, but 2 games later the man from Buenos Aires had claimed the biggest achievement of his career. Querrey has never made it past the fourth round at Flushing Meadows but could not have asked for a better chance to make a deep run at his home Slam.
Schwartzman will be a first participation in the fourth round of a major tournament.
The 37-year-old proceeded to reach the last 16 of a major for the seventh consecutive time, defeating Greece's Maria Sakkari in straight sets to line up a fourth round meeting against Spain's Carla Suarez Navarro.
The draw certainly looks more inviting to Zverev than when he reached the fourth round at the Australian Open this year. He is in the fourth round at a major for only the second time. Lorenzi, who is more at home on clay courts than hard, has been a late bloomer and only reached his first ATP final at 32; he lifted his first ATP title in 2016 at Kitzbuhel.
Seven weeks on, the result was no different as the Spaniard won by the same scoreline to set up a fourth round showdown against two-time champion Petra Kvitova, a 6-0, 6-4 victor over Caroline Garcia earlier in the day.
No. 17 seed Sam Querrey needed four sets to beat qualifier Radu Albot of Moldova 4-6, 6-2, 6-4, 6-4. Milos Raonic, ranked 11th, also pulled out of the U.S. Open before it began. His recent red-hot form now makes him one of the favourites to reach US Open final.
The 18-year-old Shapovalov said: "We're definitely making an impact".
Cilic, the highest seed in a clear bottom half of the draw, eventually paid the price for his lack of match practice after skipping the U.S. Open warm-up tournaments in Montreal and Cincinnati due to injury.
He'll play 16th seed Lucas Pouille for a place in the quarterfinals. Today was longer, but with the retirement, it was three sets, as well.
It was a landmark victory for Schwartzman, one of the smallest men on the tour at 5ft 7in, who is through to the fourth round at a slam for the first time. Carreno Busta has steadily improved over the last 16 months, and will be aiming to do one better at Flushing Meadows.