"The scope and effect of China's construction activities in the South China Sea differ from those of other countries in several key ways," Mattis told the Shangri-La regional defence summit in Singapore.
"This includes the nature of its militarisation... China's disregard for international law ... (and) its contempt for other nations' interests."
Mattis's remarks come as China builds up a series of artificial islands on shoals and reefs in contested waters in the South China Sea, which has sparked broad concern among its neighbours.
He urged regional nations to seek solutions through mediation.
"We are going to have to work together," Mattis said.
"I don't think there's room right now to pushing adversarial approaches."
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