Jo-Wilfried Tsonga, Tomas Berdych, John Isner and Alexandr Dolgopolov all progressed in matches they were, on paper, expected to win.
Top seed Tsonga downed Sergiy Stakhovsky of Ukraine 7-6(1) 6-4 to set up a last-eight clash with sixth seed Marcel Granollers, the Spaniard having beaten Latvia's Ernests Gulbis 4-6 6-3 6-2 in his second-round match.
Second seed Berdych secured a regulation 6-2 6-3 win over Finland's Jarkko Nieminen, the 16th seed, and the Czech will now play Steve Darcis for a place in the semis.
Belgian Darcis produced a shock to eliminate home favourite Roddick 7-6(6) 7-6(3).
Roddick was always in the match as both players struggled to break serve, but it was the world number 81 from Saive in Belgium that won both tie-breaks.
The American, roared on by the crowd, fought strongly in the first-set breaker, eventually losing it 8-6, but was comprehensively outplayed in the second.
There was some cheer for the home crowd though as third seed Isner saw off Juergen Melzer of Austria 6-4 6-3 to reach the quarters, where he will meet another Belgian in the shape of David Goffin, who beat Lukasz Kubot of Poland 6-3 1-6 7-6(5).
Fourth seed Dolgopolov was not overly tested by David Nalbandian as he swept through to the quarter-finals with a 6-3 6-4 win.
Dolgopolov, the world number 15, stormed through the opening set, destroying the Argentine’s serve at will, and the 14th seed could not find a response.
The Ukrainian required just a solitary break of serve in the second set to ensure a comfortable progression, with Nalbandian left extremely frustrated by his inability to force a way back into the match.
Dolgopolov will next take on seventh seed Sam Querrey, who defeated Spain’s Feliciano Lopez in their third-round match.
The American won by the same scoreline as he overcame the ninth seed comfortably, and his serve was rarely troubled as Lopez struggled to get into the match.