He stressed that the leave vote has determined the bloc's political agenda in the foreseeable future and will echo in all the decisions it will take.
"No member state has ever left the Union, so Europe is entering a period of uncertainty as the UK and the EU take stock of the situation and begin staking out their negotiating positions," he said.
Going further on this issue, CIA director said that Britons have constituted a precedent that could be followed by Eurosceptics in countries like Denmark, France, Italy and the Netherlands.
"This will surely make decision-making and forging consensus in the EU much harder."
Amid the growth of security instability worldwide, Brexit-related political turbulence in Europe could play into the hands of terrorist groups like Daesh, he added. Delivering a speech shortly after suicide bombers attacked Istanbul, the CIA head claimed that the United States could also be targeted by violent extremists.
Brennan said that he had been on the phone with his British counterpart to reaffirm "the bonds of friendship and cooperation" between the two states' agencies that are "destined to grow stronger in the years ahead."
However, Brennan admitted that the instability caused by the vote threatens "institutions and relationships that have been pillars of the post-cold war" world order and will heavily impact the security of both the Old and the New Worlds.
"I have never been witnessing a time with such a daunting array of challenges to our nation's security," he said.
The Brexit referendum was held on June 23, 2016. Roughly 52 percent of the British citizens voted to leave the European Union.
