Nick Kyrgios has just received a massive leg up in his quest for a maiden grand slam title, with 22-time major winner Rafael Nadal out of the US Open draw.

Nadal’s four set loss to No.22 seed American Frances Tiafoe, 6-4, 4-6, 6-4, 6-4, means that Kyrgios has his best shot at a major title in his career.

WATCH THE VIDEO ABOVE: Rafael Nadal knocked out of US Open.

Watch the latest sport on Channel 7 or stream for free on 7plus >>

The Spaniard botched a chance at deuce in the fourth set to break back and level at 4-4, which would have given him a fighting chance to take the match to an epic fifth set.

Tiafoe held his nerve to go up 5-3 and held his next service game to 15, knocking out arguably the greatest of all time, Nadal, who was going for his third slam this year.

The American was lost for words after the match.

“I don’t even know what to say right now,” he said in his on-court interview.

“I’m beyond happy; I’m almost in tears. I can’t believe it. I can’t believe it.

“He’s (Nadal) definitely one of the greatest of all time. I played unbelievable tennis today, but I really don’t know what happened.”

Frances Tiafoe beat Rafael Nadal at the US Open. Credit: Mike Stobe/Getty Images

The 24-year-old said he had come a long way since his first few years on tour, when he felt like he wasn’t handling the pressure of expectation.

“Honestly, when I first came on the scene, I felt like a lot of people had a lot of expectations on me of how I would do. I wasn’t ready for it, mentally, I wasn’t mature enough for the moments,” he said.

“These last couple of years, when the attention hasn’t been on me, I’ve been able to develop.

“I’m just happy with where I am with life in general. I’m able to just do me, and do it my way, and enjoy the game I love.”

Tiafoe admitted he could sense the finish line when he was serving for a 5-3 lead in the fourth set, and he couldn’t help but feel the effects of it.

Rafael Nadal is out of the US Open. Credit: Mike Stobe/Getty Images

Kyrgios loses point in bizarre circumstance.

Kyrgios loses point in bizarre circumstance.

“At 4-3, when I went up 40-0, my legs were like cement. I was like, ‘just get out of this game, just get out of this game and pray to god that you don’t have to serve for it’. I was lucky enough to get out of that game,” he said.

“I played great tennis today. I came out to win a tennis match in front of you guys”.

The American’s win means Nick Kyrgios has never had a clearer path to a grand slam win than this.

The Aussie still has No.3 seed Carlos Alcaraz and No.5 seed Casper Rudd in the draw, but does not have to worry about Nadal, Daniil Medvedev, who he beat in a scintillating four sets yesterday, or Novak Djokovic, who wasn’t allowed to enter the country because of his stubborn vaccination stance.

If Kyrgios is able to go all the way to the title, his ranking will climb inside the top 10 for the first time in his career.

His career-high ranking is currently 13.

Kyrgios faces No.27 seed Russian Karen Khachanov in the quarter finals on Wednesday morning (AEST).

Incredibly cute 9-year-old Serena’s spooky interview.

Incredibly cute 9-year-old Serena’s spooky interview.