Sakkari, the 13th seed, fought back from a set down to record a 5-7, 7-6, 6-1 victory at the Billie Jean King National Tennis Centre.

The Greek will face Britain's Johanna Konta in the quarter-finals of the joint Association of Tennis Professionals (ATP) and Women's Tennis Association (WTA) tournament, moved from its traditional home in Cincinnati to New York due to the coronavirus pandemic.

Williams had led by a set and a break before Sakkari rallied to close out an impressive win over the 23-time Grand Slam champion.

"It was tough," said Williams. 

"I literally should have won that match. 

"There was no excuse."

Konta, seeded eighth, secured her place in the quarter-finals by defeating Russia's Vera Zvonareva 6-4, 6-2.

In the men's draw, world number one Novak Djokovic beat Tennys Sandgren of the United States to cruise into the last eight.

Djokovic showed no signs of the neck pain which troubled him in his third round match with Ricardas Berankis of Lithuania as he won 6-2, 6-4 to set up a quarter-final meeting with Germany's Jan-Lennard Struff.

Defending champion Daniil Medvedev is also through after beating Slovenia's Aljaz Bedene 6-3, 6-3.

But former world number one and three-time Grand Slam champion Andy Murray is out after he lost 6-2 6-2 to world number 30 Milos Raonic.

The Western and Southern Open is usually held in Cincinnati but was moved to Flushing Meadows to create a two-tournament safety bubble, which also includes the US Open, due to begin at the same venue next Monday (August 31).

The competition is an ATP Masters 1000 event and WTA Premier 5 tournament.