The FBI chief told CBS television's "60 Minutes" program China topped the list of countries seeking to pilfer secrets from US firms, suggesting that almost every major company in America had been targeted.
"There are two kinds of big companies in the United States," Comey said. "There are those who've been hacked by the Chinese, and those who don't know they've been hacked by the Chinese."
Annual losses from cyber-attacks launched from China were "impossible to count," Comey said, but measured in "billions."
Asked which countries were targeting the United States, Comey replied: "I don't want to give you a complete list. But ... I cant tell you top of the list is the Chinese."
Comey cited the historic case of five members of China's People's Liberation Army indicted with hacking US companies for trade secrets, a move which outraged China when announced in May.
The case is the first-ever federal prosecution of state actors over cyber-espionage.
The PLA unit is accused of hacking into US computers to benefit Chinese state-owned companies, leading to job losses in the United States in steel, solar and other industries.
"They are extremely aggressive and widespread in their efforts to break into American systems to steal information that would benefit their industry," Comey said of China's hackers.
Comey said China was seeking to obtain "information that's useful to them so they don't have to invent."
"They can copy or steal to learn about how a company might approach negotiations with a Chinese company all manner of things," he said.
But China's hacking efforts were often easy to detect, Comey said.
"I liken them a bit to a drunk burglar. They're kickin' in the front door, knocking over the vase, while they're walking out with your television set," he said.
"They're just prolific. Their strategy seems to be, "We'll just be everywhere all the time. And there's no way they can stop us."
Last week, big bank JPMorgan Chase revealed that a hack it had reported in August had compromised data on 76 million household customers and seven million businesses, including their names, email addresses and telephone numbers.
Treasury Secretary Jack Lew, speaking on ABC television, declined top address the JPMorgan Chase case specifically.
But he stressed: "we have made enormous efforts to bring attention to this and resources to this. The president (Barack Obama) has taken action through an executive order.
"Look, we have a lot of concerns about the sources of attacks because there are many different sources, " Lew underscored.
"I've spoken to it publicly as recently as this summer in new York and met with CEOs in the financial sector quite financial sector quite regularly since becoming secretary. They're taking it seriously. I don't think there's a CEO in the financial sector that doesn't wake up in the morning with this on their mind.
"It's something that we have to pay attention to every day," Lew added, saying that legislation to make it easier for businesses to get on board.
In August, the Federal Bureau of Investigation acknowledged that it and the US Secret Service were investigating the scope of recent cyber-attacks against several US financial institutions.