The Chinese government "systematically dismantled" CIA spying operations in China starting in late 2010, according to The New York Times.
The paper reports that the Chinese government killed at least a dozen CIA sources and imprisoned up to eight others over the next two years. One was shot in front of his colleagues in the courtyard of a government building, according to the report.
The newspaper cites 10 current and former U.S. officials, who describe the intelligence breach as one of the worst in decades. They spoke on condition of anonymity.
The report published Saturday says U.S. intelligence and law enforcement agencies scrambled to stem the damage, but were bitterly divided over the cause of the breach.
According to the report, debates between U.S. officials were punctuated with "macabre" phone calls - "We lost another one" - and urgent questions from the Obama administration for answers.
Some investigators were convinced there was a mole within the CIA, pointing to a former employee who had remained in Asia after leaving the agency. Others believed the Chinese had hacked the covert system the CIA used to communicate with its foreign sources.
Another theory attributed the losses to "sloppy" American tradecraft at a time when the Chinese were getting better at monitoring espionage activity.
The report says some FBI agents became convinced CIA handlers too often travelled the same routes to the same meeting points. Some officers met their sources at a restaurant bugged with listening devices, where even the waiters worked for Chinese intelligence, according to the Times.
The breach predated the 2015 Chinese hack of the US government's Office of Personnel Management, in which four million current and former federal employees had their personal information stolen.
The CIA declined to comment.
In March, the CIA suffered its biggest ever data breach when WikiLeaks released a massive trove of secret documents revealing how US spies can remotely hack and control smartphones, computers, TVs and even vehicles.
A second data dump later that month showed how the CIA had been hacking iPhones and Macs for the past 10 years.