Secretary of State Rex Tillerson and Defense Secretary Jim Mattis are to meet top Beijing diplomat State Councilor Yang Jiechi and General Fang Fenghui, chief of Chinese army staff, at the State Department.
US officials said the first and main item on the agenda would be persuading China to lean on Kim Jong-Un's North Korea regime, in order to halt its provocative missile and nuclear plans.
But, just hours before the talks began, Trump sent a tweet implying that China's President Xi Jinping had already tried and failed to rein in Pyongyang.
"While I greatly appreciate the efforts of President Xi & China to help with North Korea, it has not worked out. At least I know China tried!" Trump tweeted.
Trump did not elaborate on what might happen next, and US diplomats insisted the talks would go ahead as planned, and with the same agenda.
In April, Trump hosted Xi at his Mar-a-Lago resort in Florida, glossing over his harsh campaign comments against Beijing and -- after apparently successful talks -- hailing the dawn of "a very, very great relationship."
Last month Beijing and Washington signed a limited deal to open new markets for each other's exports, and a long-standing friend of the Chinese leadership, Iowa Governor Terry Branstad, was confirmed as ambassador.
But tensions remain -- particularly over China's building of artificial islands in disputed South China Sea waters, and Washington's strong desire to get Beijing to rein in Kim Jong-Un's isolated North Korean regime.
Susan Thornton, acting assistant secretary of state for East Asian and Pacific affairs, said that the first meeting of the new "US-China Diplomatic and Security Dialogue" on Wednesday would focus on North Korea.
"We continue to urge China to exert its unique leverage as North Korea's largest trading partner, including by fully implementing all UN Security Council sanctions," she said.
Despite international condemnation and sanctions, North Korea has a small nuclear arsenal and is developing nuclear-capable ballistic missiles that threaten Japan and South Korea -- and one-day could even hit some US cities.
Washington has some 28,000 troops deployed in South Korea and a naval armada in the region.
- Prisoner in a coma -
Last week, the release of a detained US tourist in what initially seemed a gesture of goodwill by Pyongyang turned sour when it was revealed that 22-year-old Otto Warmbier had been in a coma for some time.
Warmbier died on Monday after returning to his hometown in Ohio, triggering outrage in the United States.
Trump's White House has made halting the nuclear threat its number one foreign policy priority, putting aside concerns over trade and currency manipulation to seek Beijing's help in facing down Kim.
China has tightened controls on trade in North Korean coal, but many doubt that Beijing will truly enforce any sanctions that might threaten the stability of its unpredictable neighbor.
- Isolate Kim -
"We're going to be focusing, as I said, on particularly on the urgent threat posed by North Korea, and we expect that that will take some time," Thornton said.
"We don't expect that we'll resolve that problem on Wednesday."
The chairman of the US Joint Chiefs of Staff, General Joseph Dunford, agrees that the few short weeks since the Mar-a-Lago summit was probably too short to be able to tell whether China is ready to isolate Kim.
He said Monday the Pentagon would maintain lines of communication with the Chinese military to head off any escalation in the South China Sea, but keep this separate from the diplomatic effort on North Korea.
"Secretary Tillerson has said that a key element of any success we would have in de-nuclearizing the peninsula would be the cooperation of China," he said.