Second seed Hubert Hurkacz was a shock second-round casualty from the Citi Open on Wednesday after a straight-sets defeat to Emil Ruusuvuori.
World number 46 Ruusuvuori triumphed 6-4 7-6 (7-3) in one hour and 43 minutes to book a quarter-final spot.
Hurkacz, who is ranked 11th in the world and reached last year's Wimbledon semi-finals, fought hard but failed to capitalise on four break points throughout the match.
"He had an early break point, but then I was able to keep that service game and give myself a chance to break him and I was able to use it and then just try to keep my own serve," Ruusuvuori said.
"I just tried to hang in there and tried to stay as tough as [I] can."
Wimbledon runner-up Nick Kyrgios defeated 14th seed Tommy Paul 6-3 6-4 in one hour and 25 minutes.
The Australian hit 29-21 winners, with the majority coming from his serve and forehand, sending down 15 aces, winning 84 per cent on his first serve.
Kyrgios, who broke Paul in his opening service game, converted three of four break points for the match, while the American failed to capitalise on any of his four.
Sixth seed Denis Shapovalov was bundled out in the second round by American wildcard J.J. Wolf 6-2 6-7 (5-7) 6-3 in a major upset.
Third seed Taylor Fritz avoided an early exit with a 6-4 6-4 win over Australian Alexei Popyrin in one hour and 11 minutes, while fourth seed Reilly Opelka came from a set down to defeat Denis Kudla 6-7 (6-8) 6-4 6-4 in just over two hours. Opelka sent down 28 aces across the match.
Fifth seed Grigor Dimitrov got past Adrian Mannarino 6-1 3-6 7-5 and ninth seed Holger Rune brushed off Benoit Paire 6-3 6-2.
Francis Tiafoe defeated Christopher Eubanks 6-3 7-6 (7-2), while 13th seed Maxime Cressy fought back from an early deficit to get past Jack Sock 4-6 6-4 6-0 to set up a third-round clash with top seed Andrey Rublev.
There were defeats for 11th seed Alex de Minaur to Yoshihito Nishioka 3-6 7-6 (8-6) 6-2, 12th seed Sebastian Baez against Sebastian Korda 6-1 6-4 and 15th seed Aslan Karatsev against Andy Murray's first-round conqueror Mikael Ymer 6-4 3-6 6-4.
At the Los Cabos Open in Mexico, second seed Felix Auger-Aliassime had no troubles against local Juan Alejandro Hernandez Serrano, winning 6-3 7-5.
American sixth seed Brandon Nakashima also progressed into the quarter-finals with a 6-3 6-3 win over Max Purcell, while Miomir Kecmanovic beat Jordan Thompson 6-4 6-2.