Stefanos Tsitsipas and Alexander Zverev were surprise second-round casualties at the Western & Southern Open, where Andrey Rublev set up a showdown with a seven-time champion.
Tsitsipas was sent packing following a shock defeat to Jan-Lennard Struff, while Zverev was surprisingly upstaged by Miomir Kecmanovic in three sets.
Fellow seed Kei Nishikori also exited the ATP Masters 1000 tournament but Rublev earned a meeting against Roger Federer.
STRUFF STRUTS HIS STUFF IN TSITSIPAS UPSET
Tsitsipas was tamed by Germany's Struff, who claimed a 6-4 6-7 (5-7) 7-6 (8-6) victory after two hours, 14 minutes in Cincinnati.
The Greek fifth seed managed to save three match points from 6-3 down in the third-set tie-break, but Struff was not to be denied his fifth win in his past 10 matches against top-10 opposition.
Struff's reward is a last-16 clash against Daniil Medvedev, who beat Benoit Paire 7-6 (7-2) 6-1.
ZVEREV TALLIES 20 DOUBLE FAULTS IN EXIT
World number six Zverev surrendered a lead as he went down 6-7 (4-7) 6-2 6-4 to Kecmanovic.
Zverev struggled after winning the opening set, recording a career-high 20 double faults to fall to 0-5 at the Masters event.
Kecmanovic, who reached his maiden Masters quarter-final in Indian Wells, will play 11th seed Roberto Bautista Agut for a spot in the last eight.
Spaniard Bautista Agut outlasted Frances Tiafoe 6-3 3-6 6-1. Meanwhile, sixth seed Nishikori lost to fellow Japanese Yoshihito Nishioka 7-6 (7-2) 6-4.
FEDERER AWAITS RUBLEV AFTER WAWRINKA WIN
From one Swiss to another. Russian Rublev dispatched Stan Wawrinka 6-4 6-4 to book a date with Federer.
Rublev saved all five break points against three-time grand slam champion Wawrinka.
The 21-year-old can now look forward to a first meeting with last year's runner-up Federer.
The likes of Karen Khachanov, David Goffin, Alex de Minaur and Richard Gasquet also progressed to the last 16.
