Acting Defense Secretary Patrick Shanahan takes a swipe at China.
The Defence Minister also said that his country would not "attack unless we are attacked" as both states vie for dominance in the region.
While he didn't specifically name China in early parts of his speech, he made clear who his target was, making pointed references to Beijing's campaign to put advanced weapons systems on disputed islands in the region.
A day earlier, Acting Defense Secretary Patrick Shanahan told the same gathering that the USA and China would eventually resolve their differences, downplaying the significance of escalating trade tensions even as he ripped Beijing's leaders for behavior that "sows distrust" in Asia.
"On the trade friction started by the United States: if the USA wants to talk, we will keep the door open".
Washington has been pushing back against Beijing's aggressive militarisation of the South China Sea, where China has staked "indisputable" ownership over nearly the whole area and rejects partial claims by Taiwan, Brunei, Malaysia, the Philippines and Vietnam.
Beijing is also regularly angered by United States warships transiting through the Taiwan Strait, which it considers part of its territorial waters.
At a press conference in Singapore Friday, Shanahan warned against Chinese measures to destabilize other countries.
Speaking in Mandarin at the Shangri-La Dialogue security summit in Singapore, he said: "A talk?" Wei is scheduled to speak Sunday, when he is expected to respond to Shanahan's remarks.
Shanahan said the United States was investing heavily in new military technology to combat fresh threats and maintain its superiority and capability to defend its Asian allies.
The acting secretary said the administration was committed to the Indo-Pacific region, calling the area the United States' "priority theater". "We are where we belong. We are investing in the region", he said, adding that military investments will rise significantly over the next five years. "We are investing in you, and with you", Shanahan said.
Lieutenant General Shao Yuanming, deputy chief of the Joint Staff Department of China's Central Military Commission, also slammed Shanahan's "false remarks" on the South China Sea.
While the U.S. does not seek conflict, it knows that having the capability to win wars is the best deterrence.
"We want to ensure no adversary believes it can successfully achieve political objectives through military force", Shanahan said.
He said the Pentagon has requested $104 billion globally - its most ever - for research and development in the next fiscal year, and $125 billion in operational readiness.
Shanahan's speech was however less confrontational than had been widely expected in some quarters, rejecting a suggestion during the question-and-answer question that there is a "face-off" between the USA and China. "Any foreign interference in the Taiwan issue is doomed to failure".
The two sides have been ruled separately since the end of a civil war on the mainland in 1949 but China still sees Taiwan as part of its territory to be reunified.
Wei also said that China's policies in Xinjiang had improved people's lives and prevented terror attacks from happening for more than two years. "We should welcome it, provided that everyone plays by internationally established rules". "We hope that the U.S. side will work with us towards the same goal, follow the principles of non-conflict, non-confrontation, mutual respect and win-win cooperation, and steer the China-U.S. relations in the right direction".
The second issue raised by Gen Wei was the South China Sea, where China has overlapping claims with four Asean countries.
The high-level participation by China at a summit Beijing sees as US-dominated comes at a time of growing China-US rivalry.
Shanahan said that while the United States is willing to cooperate with the regime, and welcomes competition.
"It's good that the Chinese are coming here and that they listen, but given the way that the decisions are being made now in China, the opportunities for the messaging here to get back to Xi Jinping are probably virtually none, so it's very hard to get the top guy to hear what the concerns are of the outside world".
And listening closely in the audience were nervous allies and partners in the region who are anxious about the economic impact of the U.S. "I can not afford to go to war with anybody, not only with China".