Unseeded German Jan-Lennard Struff resisted a Stefanos Tsitsipas fightback while Serbian teenager Miomir Kecmanovic beat fifth-seed Alexander Zverev as two of the bigger upsets on Wednesday at the Cincinnati Masters.
Struff, who has yet to win an ATP singles title in his decade-long career, was on top for most of the match against the 21-year old Greek.
He served for the match in the second set but Tsitsipas managed to stay alive by taking the set on a tiebreak.
However, the German refused to give up and sealed the 6-4 6-7(5) 7-6(6) victory to set up a third round meeting with ninth-seed Daniil Medvedev, who beat France’s Benoit Paire 7-6(2) 6-1.
“I had a chance to serve it out at 6-4 5-4 but he broke back and that’s the quality he has,” Struff said.
“The quality I had today was coming back from that, the chance to win the match in two sets, then at 6-3 in the (third set) tie-break and then from 6-6.
“He was playing very well. I was telling myself ‘I have to go for it, otherwise I won’t win’.
“I’ve been working hard with my team on my fitness and it’s all finally paying off and I’m playing with greater consistency.”
Struff’s compatriot Zverev was less consistent as he served a career-high 20 double faults in his 6-7(4) 6-2 6-4 defeat to the 19-year-old qualifier from Belgrade.
The second youngest player in the top 100, Kecmanovic’s victory was his first against an opponent ranked in the top 10 and he is projected to advance into the top-50 next week.
Among the other surprises on Wednesday, world number five Kei Nishikori was beaten 7-6(2) 6-4 by Japanese qualifier Yoshihito Nishioka, while Canadian Denis Shapovalov also lost 6-4 6-4 to Lucas Pouille.
World number one Novak Djokovic and third seed Roger Federer advanced to the third round on Tuesday.