On Thursday night, Botic van de Zandschulp shocked U.S. Open favorite Carlos Alcaraz in straight sets.

But what happened Friday night on Arthur Ashe was even more shocking.

For the first time since 2006, the fourth round of the U.S. Open will not feature Novak Djokovic.

Alexei Popyrin stunned the 24-time Grand Slam champion in four sets, halting his quest for a record-breaking 25th Grand Slam.

Djokovic's surprising third round defeat marks the end of a challenging year for the Serbian, who, for the first time since 2017, has failed to win a Grand Slam title in a calendar year.

Adding to the drama, the loss has left the U.S. Open bracket wide open, with two of the top three seeds missing from the fourth round for just the third time in Open Era history (1973, 2000).

Does this pave the way for an American to finally break through and end a 21-year-long drought that started on these very courts?

Here are the top reactions from Friday's play.

Friday U.S. Open Results

Men's Singles

No. 28 Alexei Popyrin def. No. 2 Novak Djokovic, 6-4, 6-4, 2-6, 6-4

No. 4 Alexander Zverev def. Tomas Marrtin Etcheverry, 5-7, 7-5, 6-1, 6-3

No. 6 Andrey Rublev def. No. 32 Jiri Lehecka, 6-3, 7-5, 6-4

No. 8 Casper Ruud def. Juncheng Shang, 6-7(1), 3-6, 6-0, 6-3, 6-1

No. 9 Grigor Dimitrov def. Tallon Griekspoor, 6-3, 6-3, 6-1

No. 12 Taylor Fritz def. Francisco Comensana, 6-3, 6-4, 6-2

No. 20 Frances Tiafoe def. No. 13 Ben Shelton, 4-6, 7-5, 6-7(5), 6-4, 6-3

Brandon Nakashima def. No. 18 Lorenzo Musetti, 6-2, 3-6, 6-3, 7-6(4)

Women's Singles

No. 2 Aryna Sabalenka def. No. 29 Ekaterina Alexandrova, 2-6, 6-1, 6-2

No. 3 Coco Gauff def. No. 27 Elina Svitolina, 3-6, 6-3, 6-3

No. 7 Qinwen Zheng def. Jule Niemeier, 6-2, 6-1

No. 13 Emma Navarro def. No. 19 Marta Kostyuk, 6-4, 4-6, 6-3

No. 33 Elise Mertens def. No. 14 Madison Keys, 6-7(5), 7-5, 6-4

Yafan Wang def. No. 20 Victoria Azarenka, 6-4, 3-6, 6-1

No. 24 Donna Vekic def. Peyton Stearns, 7-5, 6-4

No. 26 Paula Badosa def. Elena Gabriela Ruse, 4-6, 6-1, 7-6(8)

Novak Djokovic Falls in Stunning Defeat to Alexei Popyrin

Novak Djokovic suffered one of the biggest upsets in recent years, falling to Alexei Popyrin Friday night on Arthur Ashe.

The 24-time Grand Slam champion had already faced the Aussie in two other Grand Slams this year, defeating him each time in four sets.

However, Alexei Popyrin's hard work has really come to fruition this summer.

Since the Olympic games, Popyrin has accumulated a 9-1 record on hard-court surfaces, including recently lifting his maiden ATP 1000 title at the National Bank Open in Montreal, Canada.

Despite the mental challenge that comes with holding a two-set-to-love lead against Djokovic, widely considered the greatest player in tennis, the Aussie remained unshaken.

And in the crucial moments of the match, Popyrin seized the moment—a rare occurrence when facing Djokovic.

Djokovic's persistent service struggles proved to be his Achilles heel.

In defeat, the Serbian committed 14 double faults while serving just 58% on his first serve.

On Sunday, Popyrin will face Frances Tiafoe in his first Grand Slam fourth-round appearance.

Frances Tiafoe Defeats Ben Shelton in Five-Set Thriller

Frances Tiafoe waited nearly a year for this rematch.

Now he can sleep peacefully.

Nearly a year removed from suffering a heartbreaking loss in the 2023 U.S. Open quarterfinal against Ben Shelton, Tiafoe earned the ultimate revenge, defeating the talented youngster in a five-set thriller to reach the fourth round of the U.S. Open.

Despite trailing two sets to one, the 26-year-old overcame the talented youngster, using a combination of power and consistency.

In the final two sets, Tiafoe committed just seven unforced errors and won 24 of 26 points on first serve.

Additionally, in those final two sets, he grabbed two pivotal service breaks against a player who, throughout the first two rounds, had been untouchable on serve, winning 28 straight service games.

The American remains a dark horse contender and will face Alexei Popyrin in the fourth round.

Coco Gauff Escapes Tough Test, Faces Emma Navaro in Wimbledon Rematch

Coco Gauff opened up her match against Elina Svitolina, immediately struggling with her serve.

In the first set, the American won 70% of points on her first serve, but her second serve told a different story, where she won just 29% of points.

Despite dropping the first set, the defending champion found her best as the match progressed, winning 71% of service points in the second set, combined with just seven unforced errors, nine less than she committed in the opening set.

In the third set, it was Svitolina's serving that dictated the final outcome.

The Ukrainian double-faulted six times, allowing Gauff to grab three breaks on her serve.

Gauff will face American compatriot Emma Navarro in the fourth round, looking for revenge against the 23-year-old who defeated her in the fourth round of Wimbledon this year.