Serena Williams powered to a record 307th Grand Slam match win on Saturday to reach the fourth round of the US Open.

Williams moved ahead of Martina Navratilova for most match wins in a major by a woman, and tied Roger Federer's mark for men with a 6-2, 6-1 pasting of Sweden's Johanna Larsson.

The American superstar, seeking a record seventh US Open title, next faces Kazakhstan's Yaroslava Shvedova, a 6-2, 7-5 winner over China's Zhang Shuai.

Polish fourth seed Agnieszka Radwanska reached the US Open last 16 for the fifth time with a 6-2, 6-3 win over France's Caroline Garcia.

Radwanska will face either 18-year-old Ana Konjuh of Croatia or Varvara Lepchenko of the United States for a place in the quarter-finals.

Novak Djokovic reached the US Open last 16 in just 32 minutes Friday when Mikhail Youzhny retired injured before fellow two-time winner Rafael Nadal also made the fourth round for the first time in three years.

Defending men's champion Djokovic was 4-2 ahead in the first set when Russian 34-year-old Youzhny called it quits suffering from a left hamstring injury.

The outcome completed a bizarre first week for world number one Djokovic.

After labouring over four sets to beat Jerzy Janowicz on Monday, he was handed a walkover into the third round when Czech opponent Jiri Vesely withdrew from their second round clash with an arm injury.

"I have never had this happen before in my Grand Slam career, getting a walkover and the next match lasting just half an hour," said Djokovic.

The top seed next faces Britain's world number 84 Kyle Edmund who stunned John Isner of the United States 6-4, 3-6, 6-2, 7-6 (7/5) to make a Slam fourth round for the first time.

Nadal reached the fourth round for the first time since 2013 -- the year of his last New York title -- with a 6-1, 6-4, 6-2 win over Russia's Andrey Kuznetsov.

Djokovic's very brief encounter had been preceded on Arthur Ashe Stadium by women's eighth seed Madison Keys pulling off an epic comeback to beat Japan's Naomi Osaka.

Keys won the latest-ever finishing women's match at the tournament on Monday when she completed victory over compatriot Alison Riske at 1:48am.

On Friday, the 21-year-old was involved in more drama when she rallied from 1-5 down in the final set to defeat Osaka 7-5, 4-6, 7-6 (7/3).

In stark contrast, German second seed and Australian Open champion Angelique Kerber closed out the night session with a 6-1, 6-1 win in just 53 minutes against American 17-year-old CiCi Bellis.