Australian John Millman has caused the biggest upset of his career to reach his first top-tier ATP Tour semi-finals.

World No. 81 Millman shocked the world No.15 Richard Gasquet in the quarter-finals of the Winston-Salem Open 7-5 6-3 in North Carolina on Thursday (Friday AEST).

The win against the No.1 seed is Millman’s highest-ever ranked scalp and comes just days out from the US Open.

He will now face Spaniard Pablo Carreno Busta in the semi-final after he beat Andrey Kuznetsov 6-3 6-2.

“It’s been real great to play here all week, it hasn’t been easy,” Millman said.

“Richard is a great player and he makes you work so hard for every point.”

The pair traded breaks of serve throughout the first set before Millman produced a risk-free brand of tennis in the second to take out the match.

Struggling in the hotter conditions, the 28-year-old also took the unusual step of calling for a soft drink during the match for hydration.

“I just needed a little bit of boost and that was Pepsi to give me that ride,” he said.

“It’s been a long few weeks. I was at the Rio Olympics and that physically was really tough.

“You’re buzzing every day to represent your country there and then Cincinnati I played four matches there and long days with the rain.”

Millman has reached 12 second-tier ATP Challengers finals, winning eight titles.

Meanwhile Viktor Troicki and Roberto Bautista Agut will meet in the other semi-final.

Troicki came back from being a break down in the third set against Fernando Verdasco to progress 6-4 3-6 6-4, while Bautista Agut easily disposed of Yen-Hsun Lu 6-3 6-2.