Several intelligence sources told the New York Times that, beginning in 2010, the Chinese began dismantling the CIA's spy network in mainland China.
Up to 20 informants were exposed and either executed for treason — with a bullet to the back of the head — or imprisoned.
The news comes as a fresh embarrassment to the United States, which is already struggling after President Donald Trump fired FBI chief James Comey.
One Twitter user sought to link the news with revelations last year about Hillary Clinton's email server.
Reminder: #Clinton lawyer may have exposed entire server to China. How many spies were outed/killed because of this? https://t.co/uhDJGDLIX1
— Nick Short (@PoliticalShort) May 21, 2017
House Judiciary Committee chairman Bob Goodlatte, a Republican from Virginia, claimed in October that Clinton's lawyer Heather Samuelson may have allowed Chinese hackers to obtain the former Secretary of State's emails by reviewing the contents of her private server on a Chinese-made Lenovo laptop.
Mr. Goodlatte said at the time: "It seems clear that Secretary Clinton and her associates played fast and loose with our national security." But it is not clear how the Chinese managed to find out about the CIA's agents. They may have managed to turn a spy who worked as a double agent.
Yet there will be suspicion that Chinese hackers managed to somehow break through the CIA's own cyber defenses to obtain the list of agents.
From late 2010 through until the end of 2012 the Chinese reportedly killed at least a dozen CIA sources.
One was shot in the courtyard of a Chinese government building in full view of his colleagues, an act which was clearly designed to send a brutal message.
If confirmed it would be the worst intelligence failure for the CIA since Aldrich Ames began spying for the KGB in 1985, endangering the lives of dozens of informants in the Soviet Union.
In 2015, in an unrelated breach, Chinese hackers managed to get their hands on the personnel records of around four million US government employees, including people who work for the CIA and the FBI.
The New York Times said they had spoken to ten current and former officials in the US who confirmed the incident but did not want to be identified.
Last month it was reported that China's Ministry of State Security was offering Chinese citizens 500,000 yuan (US$72,000) for providing the authorities with any information on espionage activities in the country.
Andrey Karneev, deputy head of the Institute of Asia and Africa at Moscow State University, told Sputnik China previously: "The information, including facts about foreign spies bribing public servants, can be transmitted through a telephone hotline, by mail or in person by visiting an office of the Chinese Ministry of State Security."
Tensions between China and some of its neighbors — noticeably Taiwan, Japan, Vietnam, the Philippines and Malaysia — have been heightened in recent years because of disputes over islands in the South China Sea.
Edward Lin, a Taiwan-born US Navy officer is awaiting trial after being accused of spying for China.
Last week two Chinese fighter jets intercepted an American WC-135 Constant Phoenix aircraft over the East China Sea.
Earlier this month the Australian Defense Minister Dennis Richardson accused Beijing off spying on Australian soil, leading to a protestation of innocence from the Chinese government.
