"Make no mistake: The United States is in the Indo-Pacific to stay in. This is our priority theater," said Mattis.
Mattis specifically called for Beijing's militarization of artificial islands in the South China Sea, home to some of the busiest sea routes in the world.
"We are aware that China will face a series of challenges and opportunities in the coming years, we are prepared to support China's elections if they promote long-term peace and prosperity for all in this dynamic region," Mattis said.
"However, China's policy in the South China Sea contrasts sharply with the openness that our strategy promotes and puts China's broader goals in doubt," he said.
Mattis and some of his counterparts from the Asia Pacific region are in Singapore for the Shangri-La Dialogue, an annual meeting of security officials, contractors and academics in the Asian city-state.
The South China Sea has been a hot topic of discussion during the opening of the summit, amid China's attempts to badert its dominance within the strategic waters.
China, Taiwan, Vietnam, Malaysia, Indonesia, the Philippines and Brunei have competitive claims in the territory. But while other countries have built military characteristics and artificial islands, none comes close to the scale or ambition of Beijing.
Beijing claims a wide swath of territory, stretching hundreds of miles south and east from its southernmost province of Hainan.
In May, the Chinese military landed bombers with nuclear capability on their artificial islands for the first time.
Weeks earlier, US intelligence announced that there was a strong possibility that Beijing had deployed anti-ship and anti-aircraft missiles as part of ongoing military exercises.
"China's militarization of artificial features in the South China Sea includes the deployment of anti-ship missiles, surface-to-air missiles, electronic interference and, more recently, the landing of bombing aircraft on the wooded island," he said. Mattis, confirming previous intelligence reports.
"Despite China's claims to the contrary, the placement of these weapons systems is directly linked to military use for intimidation and coercion," he said.
China baderts that its actions in the South China Sea are completely peaceful and aimed at protecting its citizens and commercial interests.
Mattis only mentioned briefly the state of the Korean Peninsula in his formal comments, which occurred hours after US President Donald Trump announced that he would celebrate a summit with North Korea leader Kim Jong Un in this same city.
The Secretary of Defense remained faithful to Washington's fairly common talking points: highlighting the importance of US alliances and the ultimate goal of the complete, verifiable and irreversible denuclearization of the Korean Peninsula.
Much of the speech focused on the long-term challenges in the region known as the Indo-Pacific, a phrase used throughout India and Southeast Asia and recently adopted by the Trump administration.
Mattis also addressed the status of Taiwan, an issue that is likely to affect Beijing. China believes that the island is a renegade province and seeks its eventual reunification with the continent.
"We oppose all unilateral efforts to alter the status quo and we will continue to insist that any dispute settlement be in accordance with the will of the people on both sides of the Taiwan Strait," he said.