The two top ranked players in the world, Novak Djokovic and Andy Murray, suffered upset losses Friday, exiting the Cincinnati Masters at the quarter-final stage.
World number one Djokovic fell 7-6 (7/5), 3-6, 7-5 to unseeded John Isner as the Serb's attempt to set another tennis record ended in defeat.
Had Djokovic beaten the American he would have kept alive a bid to become the first man to win all nine Masters 1000 titles in his career.
Two-time champion Murray was eliminated 6-3, 6-4 by Tomas Berdych, leaving the Scot to head for New York and his US Open title defence from August 26 with plenty to work on.
The second seed fired 10 aces but was betrayed as he missed on all four of his break points. Berdych has now beaten Murray twice this season after defeating him in Madrid on clay.
"The court was lively today. It was bouncing pretty high and it was quite tough to control the ball. I made too many errors," said Murray, who had trouble with the conditions.
"The first couple of rounds, I was able to hit the ball quite flat and wasn't kind of flying on me; today it was happening a little bit.
"You can play one day, and in Fahrenheit it can be 65 degrees, and the next day it can be 80, 85. You just need to make adjustments. I need to make sure I'm not making too many mistakes going into the US Open."
Isner set up a Saturday semi with 2009 US Open winner Juan Martin del Potro, who beat qualifier Dmitry Tursunov 6-4, 3-6, 6-1.
Del Potro said he won despite dealing with pain in his left wrist. The Argentine missed much of the 2010 season with a wrist problems and remains cautious.
"Yes, it bothers me a little bit, but not too much," said the 2009 US Open winner.
"I'm trying to play slices and different shots before the US Open to see how different I can play against the top guys or (try) doing different things."
But he added: "I'm okay, my knee is OK too, and that's important looking forward to New York. It's nothing dangerous. I'm always in contact with my doctor; he's taking care of me all the time."
Del Potro needed one and three-quarter hours to get past veteran Russian Tursunov, with the Argentine hammering 15 aces and breaking three times. Del Potro reached the semi-finals in 2012 where he lost to Djokovic.
"This is the last tournament for me before the US Open, so it's a good thing for my preparations. I will try to play better than today."
Women's quarter-final matches were dominated by world number one Serena Williams, who raced through a 16-minute opening set en route to an easy 6-0, 6-4 win against Romanian Simona Halep.
Williams next plays holder Li Na, after the Chinese fifth seed advanced a day earlier when Agnieszka Radwanska withdrew to attend the funeral of her grandfather in Poland.
Serb former number one Jelena Jankovic beat Italy's Roberta Vinci 6-0, 6-4 to reach a fifth semi-final this season.