Greece’s fourth seed Tsitsipas Nadal is the only other top-10 player left in the draw, while fiery Australian Kyrgios is a match for anyone on his day.
Tsitsipas’ confidence has skyrocketed after winning his first grass-court title in Mallorca last week, but he faces a man he has defeated just once in his four meetings.
Kyrgios, who came out on top last month at the two-player’s Halle, is making waves on and off the court at Wimbledon.
His early victory over Britain’s Paul Jubb was fueled by his admission that he spat in the direction of fans, whom he accused of being abusive, and he also took aim at officials.
The 27-year-old, who was fined $10,000 for Tuesday’s incidents, has been in a testy mood even at the post-match press conference, but has remained fast.
“I feel like I’m comfortable in my own skin,” the 40th-ranked player said after his straight-sets win over Filip Krajinovic.
“Some people just like to tear me apart. That’s not possible anymore.”
Tsitsipas, who reached the fourth round in 2018, said he was “thrilled” to face Kyrgios, who defeated Nadal in the quarterfinals in 2014.
“I have a lot of respect for what he is trying to do on the court,” he said. “Although he’s been a little controversial in the past, I think he’s playing good tennis.”
Kyrgios’ win would give him his 10th win on grass this season.
Second seed Nadal, chasing a calendar Grand Slam, knows he has yet to scale heights at the All England Club after two poor performances so far.
“I haven’t played much on the grass in three years,” the 22-time Grand Slam winner said after his four-set win against Ricardas Berankis.
“It gives me a chance to keep going, so happy for that.
“I need to improve. I have to keep working, be humble, even when things aren’t going well.”
Australian 19th seed Alex de Minaur defeated British wild card Liam Brody 6-3, 6-4, 7-5 and will play Chile’s Christian Garin in the last 16.
Dutch 21st seed Boutique van de Zandschulp saw off a challenge from French legend Richard Gasquet in four sets.
– Tan moves on – In the women’s competition, Harmony Tan, who knocked out Serena Williams in the first round, beat British wild card Katie Boulter 6-1, 6-1 in just 51 minutes to reach the fourth round .
The 24-year-old Frenchman broke the bolter five times in an impressive performance to disappoint the crowd on Court Two.
“I guess I like grass,” said Tan, ranked 115 in the world. “I never play on this court but I like to play with my game with slices and volleys and everything so I am really happy.
“It was really emotional for the first round against Serena and it was just playing match by match and really good tennis today. I don’t know why but it depends on the day.”
Tan will next take on 20th seed Amanda Anisimova, who defeated French Open finalist Coco Gauff 6-7 (4/7), 6-2, 6-1 to return to the All-American bout.
In 2019, champion Simona Halep advanced to the last 16 with a 6-4, 6-1 win over Magdalena Frech.
World number one Iga Swiatek is aiming for a 38th straight win against unseeded French legend Alize Cornet.
The Polish top seed was asked if her winning streak has boosted her confidence, she said it didn’t come to her mind when she was playing the match.
“I’m just trying to figure out what to do better and how to come back,” she said. “So it doesn’t really matter to me.”
Fourth-seeded Paula Badosa will take on former two-time champion Petra Kvitova in one of the most exciting rounds of the third round.