"I don't know whether or not Syria and Iraq can be put back together again. There's been so much bloodletting, so much destruction," Brennan told the CTC Sentinel
, a publication of the Combating Terrorism Center at West Point.
"I question whether we will see, in my lifetime, the creation of a central government in both of those countries that's going to have the ability to govern fairly," he added in the interview which was published Wednesday.
While Brennan has previously called into question Syria's long-term stability, his comments about Iraq, where the government in Baghdad has been a key ally in the fight against ISIS, are likely to rankle officials there.
The US has long called for a unified Iraq, despite sectarian divisions that have led some to recommend a partitioned state.
Brennan raised the possibility of autonomous regions being established in Iraq in lieu of centralized government control, adding that "to have representative governments, something akin to a Western-style democracy, is going to be difficult."
In addition to supporting a centralized Iraqi state, the US has opposed the creation of autonomous zones in Syria.
"We do not believe the answer is self-autonomous rule in certain zones," State Department spokesman John Kirby told reporters about Syria in March.
The wide-ranging interview with Brennan was co-conducted last month by CTC Sentinel Editor in Chief Paul Cruickshank, who is also a CNN terrorism analyst, at CIA headquarters in Langley, Virginia. It touched on a variety of issues concerning the evolution of the terror threat in the 15 years following the 9/11 terror attacks.
Brennan said that compared to al Qaeda, ISIS is a lot less "deliberate" in its planning and more "free-wheeling," willing to carry out attacks on shorter notice.
"You look at 9/11 and other major attacks, and it was very deliberate, methodical, a lot of planning went into it. I think ISIL tries to move from idea to bang within months or within weeks," Brennan said, using the administration's preferred acronym for ISIS.
Brennan also said ISIS members are younger and better able to exploit technology to aid their terrorist activities.
"The younger you are these days, the more adept you are at being able to use very sophisticated and leading-edge apps for your activity," Brennan said.
He noted that ISIS has used chemical weapons on the battlefield in Syria and did not rule out the terror group using such weapons in its global attacks.
"I would not put anything past these individuals who are so depraved and are dedicated to mayhem and carnage," Brennan said.
The CIA chief also highlighted the long-term problem of foreign fighters, calling them "astronomical" in number and saying, "Those not killed in the fighting are going to present a challenge for our governments for years to come."
And while Brennan noted that ISIS and al Qaeda have engaged in a rivalry in Syria and elsewhere and described them as "visceral enemies," he also said that in war-torn Yemen the two terror groups were working together on local issues where they face shared enemies.