A day after hurting his left wrist in a crash in the fourth stage, Froome fell again early on the 152.5-kilometer (94.5-mile) route from the Belgian town of Ypres to Arenberg-Porte du Hainaut in France on Wednesday, scraping his right side.
Then, just before the first patch of cobblestones about halfway through the treacherous route, the Team Sky rider took another spill. With a cut under his right eye, he limped over to a team car, climbed in and left the race.
The team wrote on Twitter after his withdrawal: “Heartbreak for Chris Froome after another hard crash.”
Riders were flying left and right on the difficult stage, and one even hurtled head-first over his handlebars on a cobblestone patch.
Marcel Kittel of Germany, the winner of three of the first four stages, also went down. Belgian Juergen van den Broeck and American Andrew Talansky crashed, as well, but they remained in the race.
The withdrawal of Froome, the main pre-race favorite, leaves the three-week cycling showcase wide open.
Froome had said before the stage that the biggest concern about the seven cobblestone patches on Wednesday's route was not riding over them, but the nervousness of the pack as riders jockeyed to get up front, which is considered the safest place to be.