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6 year oldSpeaking in Singapore, General Mattis said Beijing's actions called into question its broader goals.
A Chinese military official dismissed the comments as "irresponsible".
Six countries have competing claims in the sea, but tensions have increased in recent years and China has backed its claim with island-building and patrols.
Mr Mattis also said the issue of US troops in South Korea was "not on the table" at this month's summit with North Korea's Kim Jong-un.
The US wanted complete denuclearisation of the Korean peninsula, he added.
South Korean Defence Minister Song Young-moo also told the Shangri-La Dialogue security summit that US forces in South Korea was a "separate issue from North Korea's nuclear issue".
There are currently about 28,500 US troops based in South Korea.
Mr Mattis told the security summit that Beijing had deployed military hardware including anti-ship missiles, surface-to-air missiles and electronic jammers to locations across the South China Sea.
"Despite China's claims to the contrary, the placement of these weapon systems is tied directly to military use for the purposes of intimidation and coercion," Gen Mattis said.
Gen Mattis said the Trump administration wanted a constructive relationship with China but would compete vigorously if necessary.
He also said the US recognised that China had a role to play in the region.
But speaking at the same conference, China's Lt Gen He Lei said: "Any irresponsible comments from other countries cannot be accepted."
Beijing's actions were aimed at "national defence", he added in quotes reported by AFP.
The South China Sea, a key trade route, is subject to overlapping claims by China, Vietnam, the Philippines, Malaysia, Taiwan and Brunei.
China has been building small islands and other maritime features into military facilities there.
Last month China said it had for the first time landed bombers on Woody Island in the Paracel Islands, prompting US warnings that it was destabilising the region.
Woody Island, which China calls Yongxing, is also claimed by Vietnam and Taiwan.
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