Li Shangfu's comments came a day after US and Chinese military vessels sailed close to each other in the flashpoint Taiwan Strait, an incident that provoked anger from both sides.
"Attempts to push for NATO-like (alliances) in the Asia-Pacific is a way of kidnapping regional countries and exaggerating conflicts and confrontations," Li told a security conference in Singapore also attended by US Defense Secretary Lloyd Austin.
Li warned that these alliances would "plunge the Asia-Pacific into a whirlpool of disputes and conflicts".
Li's comments echoed long-held Chinese criticism of the United States' efforts to shore up alliances in the region and counter China's rise.
The United States is a member of AUKUS, which groups it with Australia and Britain.
Washington is also a member of the QUAD group, which includes Australia, India and Japan.
"Today's Asia-Pacific needs open and inclusive cooperation, not buddying up into small cliques," Li said at the Shangri-La Dialogue security summit.
Li sought to paint the United States as the trigger of regional instability, and China as seeking to ease tensions.
"It cannot be denied that if a fierce conflict or confrontation occurs between China and the United States, it would bring unbearable pain for the world," he said.
- Miscalculations -
On Saturday, Austin called for top-level defence talks with Beijing to prevent miscalculations.
"The more that we talk, the more that we can avoid the misunderstandings and miscalculations that could lead to crisis or conflict," Austin said.
Also on Saturday, the United States deployed a destroyer from its 7th Fleet along with a Canadian naval vessel through the Taiwan Strait.
China responded by sending one of its naval ships close to the US destroyer, the USS Chung-Hoon, according to the Pentagon.
The strait is one of the world's most tense potential military flashpoints.
China claims Taiwan as its territory -- vowing to take it one day, by force if necessary -- and has in recent years ramped up military and political pressure on the island.
Austin on Sunday described the incident as "extremely dangerous", saying the Chinese vessel crossed "probably 150 feet (46 metres)" in front of the Chung-Hoon.
"I call upon the (Chinese) leadership to really do the right things to rein in that kind of conduct, because I think accidents can happen that could cause things to spiral out of control," Austin told reporters in Singapore.
Saturday's Taiwan Strait encounter followed what the US military said was an "unnecessarily aggressive maneuver" by one of Beijing's fighter's near a US surveillance plane in the South China Sea last week.
Li told the Singapore audience on Sunday that the onus was on the United States to pull its military presence away from areas near China.
"Our Chinese military aircraft and warships won't ever go near the airspace and territorial waters of other countries to engage in so-called navigational hegemony," Li said.
"The best thing would be if all countries, and especially their warplanes and warships, refrained from wandering through other country's territorial airspace and waters. What are you hanging around here for?"
Austin and Li shook hands and spoke briefly at the Singapore event's opening dinner on Friday, but there was no substantive exchange.
The United States had invited Li to meet with Austin on the sidelines of the conference, but China declined.
A senior US defense official told journalists Sunday that the US had also offered lower level meetings but that China didn't respond.
A member of China's delegation told AFP that the removal of US sanctions on Li was a precondition for talks.
However, there have been some signs of improved dialogue between the two nations.
CIA Director William Burns made a secret trip to China last month, a US official announced on Friday.
Assistant Secretary of State for East Asian and Pacific Affairs Daniel Kritenbrink will also travel to China on Sunday for a rare visit.
In his speech in Singapore on Saturday, Lloyd outlined Washington's extensive partnerships in the region.
"America's partnerships are bringing the region closer together to help keep it free, open, and secure," he said.
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