Whitfield suffered minor injuries after careening off his bike into a curb and metal guard-rail. He received stitches in his left foot, according to a team official.
Competing in his fourth and final Games, the 37-year-old was in good position following a 1.5-kilometre swim but lost control of his bike after going over a small speed bump coming out of the transition.
Whitfield appeared to be trying to slip his bare feet into bike shoes when he veered sharply to the left and was thrown into a barrier lining the central London course. He knocked another competitior down in the process.
After scrambling back to his bike, Whitfield pulled out of the race.
A number of Canadian athletes took to Twitter with messages of condolence. Marathoner Reid Coolaset thought Whitfield had the potential to step on the podium.
"The reason why it sucks so much that @simonwhitfield crashed out is because he's in great shape and was ready for a big one," Coolaset wrote on Twitter.
Dylan Wykes, another Canadian marathoner, said it was "devastating" to see Whitfield crash out of the race.
The Victoria resident is one of the top figures in the sport, having won gold at the Sydney Games in 2000 and taken silver in Beijing four years ago. He was Canada's flag-bearer during the opening ceremony in London.
However, these proved to be a tumultuous Games for Whitfield. After teammate Paula Findlay finished last in the women's triathlon over the weekend, he had sharp criticism for Triathlon Canada officials, whom he accused of botching her preparation.
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