It was not clear whether the Central Intelligence Agency (CIA) was hacked or whether a mole helped the Chinese to identify the agents, officials told the New York Times.
The CIA has not commented on the report, the BBC said on Sunday.
One of the informants was shot in the courtyard of a government building as a warning to others, the NYT report quoted an official.
Four former CIA officials spoke to the NYT, telling it that information from sources deep inside the Chinese government started to dry up in 2010. Informants began to disappear in early 2011.
The CIA and Federal Bureau of Investigation (FBI) teamed up to investigate the events in an operation one source said was codenamed Honey Badger.
The NYT report said this investigation had centred on one former CIA operative but there was not enough evidence to arrest him. He now lives in another Asian country.
In 2012, an official at China's Security Ministry was arrested on suspicion of spying for the US. He was said to have been lured into the CIA.
No other such arrests appear to have reached public attention during that time.
Matt Apuzzo, a New York Times journalist who worked on the story, told the BBC: "One of the really troubling things about this is that we still don't know what happened."
"There's a divide within the American government over whether there was a mole inside the CIA or whether this was a tradecraft problem, that the CIA agents got sloppy and got discovered, or whether the Chinese managed to hack communications," Apuzzo said.
A few years later in 2015, the CIA pulled staff out of the US embassy in Beijing, after a hack blamed on the Chinese state exposed information about millions of US federal employees.
If the events of 2010-2012 were helped by a similar hack, it was not one that was made public.
The disappearance of so many spies damaged a network it had taken years to build up, the New York Times report said, and hampered operations for years afterwards.
It even prompted questions from within the Barcak Obama administration as to why intelligence had slowed.
Officials said it was one of the worst security breaches of recent years.
(This story has not been edited by Social News XYZ staff and is auto-generated from a syndicated feed.)
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