NEW YORK (AFP) — Australia's Nick Kyrgios sent defending champion Daniil Medvedev tumbling out of the US Open on Sunday as US teenager Coco Gauff reached the quarterfinals for the first time.

The notoriously temperamental 23rd-seeded Kyrgios produced some scintillating shot-making on his way to a superb 7-6 (13/11), 3-6, 6-3, 6-2 win over the world No. 1 from Russia.

Kyrgios, who was beaten by Novak Djokovic in the Wimbledon final in July, showed grit and composure to save three set points in the opening set before holding his nerve to win an epic tiebreak 13/11 before a raucous Arthur Ashe Stadium crowd.

Although he dropped in the second set, he roared back to dominate Medvedev in the third and fourth sets to clinch victory in two hours and 53 minutes.

"It was an amazing match, obviously Daniil as the defending champion had a lot of pressure on his shoulders, but I've been playing amazing the last couple of months," Kyrgios said after the win.

"What a place to do it — packed house in New York. I'm extremely blessed."

Kyrgios will face Karen Khachanov in the quarter-finals on Tuesday. Khachanov matched his best performance in a Grand Slam event by defeating Spanish 12th seed Pablo Carreno Busta in a three hour and 21-minute five-set thriller.

The 27th-seeded Khachanov dug deep to down Carreno Busta 4-6, 6-3, 6-1, 4-6, 6-3 on the Louis Armstrong Stadium.

Elsewhere in the fourth round, fifth seed Casper Ruud became the first Norwegian to reach the US Open quarterfinals with a 6-1, 6-2, 6-7 (4/7), 6-2 victory over French lucky loser Corentin Moutet.

The 23-year-old Ruud, seeded fifth, will face Italy's Matteo Berrettini for a place in the semi-finals.

Berrettini extended his impressive run of recent Grand Slam singles performances with a 3-6, 7-6 (7/2), 6-3, 4-6, 6-2 defeat of Spain's Alejandro Davidovich Fokina.

The 26-year-old from Rome missed Wimbledon earlier this year after testing positive for Covid-19, and was injured for the French Open.

But Berrettini has now made the quarterfinals or better in the last five Grand Slams he has played in after Sunday's win.

"It's not a secret for me the Slams are the goal of the season," he said.

"I think it proves that my level is high in Slams. I play my best tennis in the most important stages of the tour."

In the women's draw meanwhile, rising American star Gauff kept home hopes alive with a battling 7-5, 7-5 win over China's Zhang Shuai on the Arthur Ashe Stadium.

The 18-year-old 12th seed will now play France's in-form Caroline Garcia for a place in the semifinals.

"I think she's playing the best tennis she's played in a long time," Gauff said of her quarterfinal opponent.

"It's going to be a challenge. When you play these players that are hot, I think it's more of a mental challenge. You just got to accept she's going to hit some great shots, because I know she will."

Garcia, the world No. 17, has emerged as a dark horse in New York despite a modest record in Grand Slams.

The 28-year-old reached her only other Grand Slam Last Eight on home ground at Roland Garros five years ago.

But she arrived in New York brimming with confidence after claiming the Cincinnati Masters lead-in event, and so far at the Open has yet to drop a set and has lost serve only twice.

Garcia says she is reaping the benefits of a more positive approach to tennis.

"To get wins, definitely helps to be happy, to know which way you have to play, to be healthy, it's a lot of positives," she said.

"I like to play tennis aggressive, to move forward. I'm having fun, enjoying playing that way, and on top of it I'm glad it's working and it's a good way for me."