Serena Williams moved within three wins of achieving the fourth women's calendar-year Grand Slam by routing fellow American Madison Keys on Sunday and setting up a US Open quarterfinal clash with sister Venus.

The American Serena beat her 20-year-old compatriot Keys 6-3, 6-3 in 68 minutes to book a 27th professional career showdown with her older sister, who advanced with a 6-2 6-1, 50-minute fourth-round victory over qualifier Anett Kontaveit, 19, of Estonia.

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Three-time defending champion Serena holds a 15-11 advantage in the sisterly head-to-head series against Venus, splitting their four previous clashes at the US Open.

Top-seeded world number one Serena has won six of the last seven matches against Venus, who beat her younger sister last year in the semifinals in Montreal.

Venus, whose last slam triumph came at the 2008 Wimbledon, said she thought she was playing well enough to win her third US Open title. "Of course. I'd love to," she said. "But it's easier said than done."

Serena brought her A-game against Keys, dropping just six points on serve in the first set.

Serena cracked six aces and never faced a break point in beating the power-hitting Keys, who put up a strong fight in their only previous meeting, in this year's Australian Open semi-finals.

Keys lost 7-6 (7-5), 6-2 in Melbourne, saving seven match points in the second set before succumbing.

This time, Serena played her strongest match of the tournament so far and Keys contributed to her loss.

Keys double faulted on the last two points of the eighth game for the lone break of the first set, and double faulted again on match point.

Serena, winner of 21 Grand Slam singles titles including the 2015 Australian Open, French Open and Wimbledon championships, currently holds all four grand slam titles, a "Serena Slam" she has now twice accomplished.

Winning this time at Flushing Meadows for her seventh US Open crown would give her the rare calendar-year Grand Slam that would match Maureen Connolly (1953), Margaret Court (1970) and Steffi Graf (1988).

In the men's singles, top seed Novak Djokovic was made to work hard by Spain's Roberto Bautista Agut before he posted a 6-3, 4-6, 6-4, 6-3 win at the US Open, moving him into his 26th consecutive Grand Slam quarterfinal.

After Djokovic won an opening-set groundstroke battle with steady accuracy and well chosen forays to the net, Bautista Agut used his big forehand to come back from 4-2 down in the second and win the next four games to level the match.

The world number one smashed his racquet after losing the second set but made better use of its replacement, winning the third following a service break in the fifth game, before raising his performances in the fourth set to claim victory.

"Congratulations to Bautista for hanging in there, for fighting. It was a great match tonight," said the Serb, winner of this year's Australian Open and Wimbledon titles.

The Spaniard unleashed 34 winners, including 22 from the forehand, but came up short in a quest to reach his first grand slam quarter-final.

"He made me work for every point," said Djokovic, who will meet Spain's Feliciano Lopez, who beat Italy's Fabio Fognini 6-3 7-6 (7-5) 6-1, in the quarterfinals.

Only Jimmy Connors (27) and Roger Federer (36) have registered more consecutive Grand Slam quarterfinal appearances in the Open era.

Defending champion Marin Cilic was the first man through to the US Open quarterfinals on Sunday, taking down determined Frenchman Jeremy Chardy 6-3, 2-6, 7-6 (7-2), 6-1 to extend his Flushing Meadows win streak to 11 matches.