Former world number one Novak Djokovic and reigning Cincinnati Masters champion Grigor Dimitrov advanced, while Alexander Zverev was bundled out.
Wimbledon champion and 10th seed Djokovic overcame a slow start to reach the last 16 with a win over Adrian Mannarino on Wednesday.
Dimitrov opened his title defence by prevailing against Mischa Zverev, whose younger brother and third seed Alexander suffered a shock second-round defeat midweek.
There were also wins for seeds Kevin Anderson, Marin Cilic and David Goffin, while Stan Wawrinka was too good for Kei Nishikori.
The clash between Juan Martin del Potro and Hyeon Chung failed to get underway due to rain.
DJOKOVIC FINISHES FAST TO ADVANCE
The 13-time grand slam champion continued his quest for a maiden Cincinnati title with a 4-6 6-2 6-1 victory.
Djokovic – a five-time finalist at the ATP Masters 1000 event as he seeks to become the first man to complete the Career Golden Masters – was sloppy early but recovered by break five times en route to victory.
"I think it adds more to the motivation rather than pressure," the 30-time Masters champion said. "I really want to win this tournament, and I have been trying. I'm still in the tournament this year, and hopefully I can get a shot at the title."
It does not get any easier for Djokovic, with Dimitrov waiting in the next round.
Fifth seed Dimitrov – who has only won one of the past nine meetings against Djokovic – topped Mischa Zverev 7-6 (7-5) 7-5.
ZVEREV STUNNED BY HAASE
There was a major shock in Cincinnati, where Alexander Zverev went down 5-7 6-4 7-5 to Robin Haase.
A beaten quarter-finalist at the Rogers Cup last week, Zverev is still waiting for his first main-draw victory at the tournament following four defeats.
Haase will play Pablo Carreno Busta for a spot in the quarters after the 13th seed defeated Bradley Klahn 6-4 6-4.
CILIC MAKES WINNING RETURN
Australian Open runner-up and world number seven Cilic outlasted qualifier Marius Copil 6-7 (4-7) 6-4 6-4. Cilic – who will take on Karen Khachanov – was playing his first Cincinnati match since winning the title in 2016.
South African sixth seed Anderson and 11th seed Goffin will go head-to-head in the round of 16. Anderson trumped Jeremy Chardy 7-6 (8-6) 6-2, while Goffin rallied past Benoit Paire 5-7 6-4 6-2.
Elsewhere, three-time major champion Wawrinka beat Nishikori 6-4 6-4 and Kyrgios claimed a 7-6 (7-1) 0-6 6-3 victory against Borna Coric.
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