In an interview with ABC television's "This Week," Holder called the alleged cooperation between expert bomb-makers in Yemen and jihadists fighting in Syria's civil war a "deadly combination."
ABC News, citing unidentified sources, said US intelligence suspects Yemeni bomb makers in Syria have designed an explosive device small enough to fit in a laptop computer.
"I think we are at a dangerous time," Holder said, referring to the linkup of experts with technical know-how and "people who have this kind of fervor to give their lives."
"It's something that gives us really extreme, extreme concern," he added in the interview broadcast on Sunday.
"In some ways, it's more frightening than anything I think I've seen as attorney general."
Holder expressed "great concern" about the influx of Europeans and Americans into Syria to fight and the "potential impact" they could have back in their home countries. He estimated there are about 7,000 such fighters at this time.
And "it's just a matter of time" before Islamic State fighters who have launched a vast offensive in Iraq and seized a large chunk of territory there set their sights toward the West and the United States "in particular," Holder added.
"So this is something that we have to get on top of and get on top of now."
Holder said the foreign fighter problem presented a clear and present danger.
"We are at a dangerous time," he said.
Holder said he was especially concerned about "lone wolf"-type militants who conduct attacks such as the April 2013 Boston Marathon bombings.
"These lone wolves, these homegrown violent extremists are people who keep me up at night, as well, trying to monitor them, trying to anticipate what it is that they are going to do," he said.
"And, you know, the experience that we had in Boston is instructive. It only takes one or -- or two people to really do something horrific."
- Air travel threat -
Holder's comments come in the wake of increased security for flights heading to the United States.
Earlier this month, US authorities announced new security measures for air passengers from Europe and the Middle East. As
part of the new security protocol, smart phones and electronic devices must be able to be switched on before travel.
The tighter security was introduced due to fears that militants linked to Al-Qaeda are developing new explosives that could be slipped onto planes undetected.
ABC cited a source at the US Department of Homeland Security as saying the unspecified threat was "different and more disturbing than past aviation plots."
In November 2010, the Yemen-based Al-Qaeda in the Arabian Peninsula, claimed responsibility for a plot to send parcel bombs to the United States.
AQAP also claimed it put a bomb aboard a UPS cargo plane that crashed two months earlier in the Gulf emirate of Dubai, killing the craft's two pilots.
The man thought to be behind that plot, master Al-Qaeda bomb maker Ibrahim al-Asiri, is currently believed to be hiding out in Yemen's restive southern provinces.
Al-Asiri, a 32-year-old Saudi citizen, specializes in building hard-to-detect non-metallic explosives, often using Pentaerythritol tetranitrate, or PETN, and chemical detonators.
US President Barack Obama warned last month that "battle-hardened" Europeans who embrace jihad in Syria threaten the United States because their passports mean they can enter the country without a visa.