New York, NY, USA, 4 September 2016 | Darren Walton/AAP

Nick Kyrgios is out of the US Open after Australia’s last singles hope was forced to retire from his third-round match against Illya Marchenko with a hip injury.

Kyrgios was trailing two sets to one – 4-6 6-4 6-1 – when he called it quits.

The 14th seed complained of the injury during his first two matches and said he felt like he’d been “hit by a bus” at one point during Saturday’s defeat.

The loss was Kyrgios’s first in 21 matches against unseeded opponents at Grand Slam events and will come as a bitter disappointment for the 21-year-old who had high hopes at the Open.

There was no sign of any trouble early on as Kyrgios broke Marchenko on the Ukraine’s first service game.

He then held from 15-40 to consolidate for a 3-0 lead, the only break he needed to secure the opening set.

At times he toyed with the world No.63, producing a series of nonchalant backhand-down-the-line winners to appear in cruise control.

Kyrgios lit up Arthur Ashe Stadium when he ran down a drop shot and conjured an incredible around-the-net-post backhand winner in the fifth game of the third set.

Out of nowhere, though, Kyrgios dropped serve at 4-4 after a double-fault and forehand miss to hand Marchenko the chance to put the match back on level terms.

He made no mistake as Kyrgios’s movement began to diminish.

After all but conceding the third set in 34 minutes, two courtside treatments from the trainer didn’t help Kyrgios.

“It’s not going to get better by playing, I guess,” a dejected Kyrgios said later.

“It’s tough. I don’t like to retire. It’s probably like the second or third time I’ve done it.

“It’s never easy, of course. I’ve got a lot of belief in my game to still win matches when I’m not feeling great.

“(But) his strength is to make balls move you around. It’s not great.

“I mean, to be fair, my hip was bothering me my first two matches and I got through. I guess it was just a matter of time.”

Kyrgios’s injury places him in doubt for Australia’s Davis Cup play-off with Slovakia in Sydney from 16-18 September.

Marchenko admitted it was not the way he wanted to reach the last 16 of a slam for the first time, five days shy of his 29th birthday.

“I feel sorry for Nick,” he said.

“But it’s a dream come true. A win is a win and a win here on Ashe is a very special feeling for me. I cannot explain how happy I am.”

The Ukraine will play two-time Grand Slam champion and third seed Stan Wawrinka on Monday for a place in the quarterfinals.