Top seed Dominic Thiem was dumped out of the Citi Open by Kevin Anderson on Thursday but Kei Nishikori and Milos Raonic progressed to the quarter-finals.
Seeded number one at an ATP Tour tournament for the first time, Thiem's campaign came to an end following a 6-3 6-7 (6-8) 7-6 (9-7) loss to Anderson.
Rain delays proved disruptive for Thiem, who failed to serve out for the match at 5-4 in the final set before watching Anderson save a match point in the tie-break.
Anderson also had the chance to wrap up the match in the second but Thiem thwarted the South African at 6-5 in the breaker, but he could do nothing a set later as Anderson served out for the match.
"It feels great. I've worked really hard and committed myself to playing the kind of tennis I want to play," said Anderson.
"I could do that on the practice court and sometimes struggled to bring it to the match court, but now I'm succeeding with that more often.
"Obviously each day presents a new challenge, but I look forward to each one and I'm much more confident overall."
His next challenge is Indian qualifier Yuki Bhambri after he beat Guido Pella 6-7 (5-7) 6-3 6-1.
Japanese second seed Nishikori emerged triumphant in his clash against Juan Martin del Potro, winning 6-4 7-5, he will face Tommy Paul in the last-eight after he shocked Gilles Muller 6-7 (3-7) 6-4 6-3.
Canadian third seed Milos Raonic's quest for a second Citi Open title continues after he saved a pair of set points as he overcame Marcos Baghdatis.
Next up for 2016 Wimbledon finalist is eighth-seeded American Jack Sock, who defeated countryman Jared Donaldson 7-6 (8-6) 6-2.
Grigor Dimitrov was a surprise casualty on Thursday, the fourth seed upstaged 6-4 6-2 by Daniil Medvedev.
Alexander Zverev is next after the fifth seed downed Tennys Sandgren 7-5 7-5.