The Austrian, chasing his first Grand Slam title, recorded a 6-2, 6-2, 3-6, 6-3 victory to knock out the 2014 US Open champion on the Arthur Ashe Stadium court at Flushing Meadows.

Thiem will next play promising Canadian Felix Auger-Aliassime, the 15th seed who thrashed Corentin Moutet of France 6-1, 6-0, 6-4.

"Today was a good win against a great champion, so that should give me a boost," Thiem said.

"I'm not 100 per cent yet. 

"I still have to raise my level if I want to go deeper. 

"I'm normally capable of doing this in the Slams [and] hopefully here as well."

Two more seeds fell in the men's draw on day six as Roberto Bautista Agut of Spain and Russian Karen Khachanov both crashed out.

Eighth seed Bautista Agut was beaten 7-5, 2-6, 4-6, 6-3, 6-2 by Canadian Vasek Pospisil, while 11th seed Khachanov lost 6-4, 0-6, 4-6, 6-3, 6-1 to Alex de Minaur of Australia.

There were no such problems for Italian sixth seed Matteo Berrettini, who despatched Norwegian 30th seed Casper Ruud 6-4, 6-4, 6-2.

In the women's draw, second seed Sofia Kenin of the United States overcame Tunisia's Ons Jabeur 7-6, 6-3 to set up a meeting with Belgium's 16th seed Elise Mertens, who ousted 18-year-old American Caty McNally 7-6, 6-3.

Alize Cornet of France also progressed after American opponent Madison Keys retired hurt when trailing 7-6, 3-2.