The synthetic opioid, many times more powerful than heroin, has caused an epidemic of addiction in the United States -- responsible for 100,000 overdose deaths a year, officials say.
Washington's allegations that Beijing is complicit in the trade have long been yet another source of contention between the United States and China, at loggerheads in recent years over everything from trade to human rights and the self-ruled island of Taiwan.
At a summit in November, presidents Xi Jinping and Joe Biden agreed to do more to cooperate on tackling companies that manufacture the precursor chemicals to make fentanyl and on cutting financing for the trade.
On Tuesday, a Washington delegation led by Deputy Homeland Security Advisor Jen Daskal arrived in Beijing for the inaugural meeting of a counter-narcotics cooperation working group.
She is accompanied by high-level US officials from the State Department, Treasury, Department of Homeland Security and Justice Department.
Calling the meetings "a good start" US National Security Council spokesman John Kirby told reporters there is still "a lot more work to be done."
"The goal here is to create concrete, measurable actions that lead to a reduction of the precursor chemicals that are killing so many Americans," he said.
Chinese Minister for Public Security Wang Xiaohong, who greeted the US delegation at Beijing's Diaoyutai guesthouse, said establishment of the China-US working group represented an "important common understanding" reached by the presidents last year.
"Our cooperation once again shows that the China-US relationship gains from cooperation and loses from confrontation," he said, speaking through an interpreter.
Wang said he hoped future meetings would see two sides "accommodating each other's concerns to enhance and expand cooperation to provide more positive energy for stable, sound and sustainable China-US relations".
Daskal in turn characterised Washington's sending the high-level delegation as a signal of its intent at a "whole-of-government approach to tackling the global challenge".
- 'Zero tolerance' -
The United States says it hopes the talks will "provide a platform to facilitate ongoing coordination designed to tackle the illicit production, financing, and distribution of illicit drugs".
Xi pledged during his summit with Biden in November to clamp down on the trade.
He also said that China "deeply sympathises" with victims of fentanyl.
The US Drug Enforcement Agency (DEA) has previously described China as "the main source for all fentanyl-related substances trafficked into the United States".
And in October, the US Justice Department slapped sanctions on more than two dozen China-based entities and individuals alleged to be the "source of supply" for many US-based narcotics traffickers, dark web vendors, virtual currency money launderers and Mexico-based criminal organisations.
Beijing has denied complicity in the deadly trade, touting its "zero tolerance" drug policies and insisting the roots of the addiction crisis lie in the United States.
Since the summit China has shut down one company, blocked some international payments and resumed sharing information on shipments and trafficking, a US official said last week.
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