The EU's foreign policy chief says the collapse of the Western-backed administration and a subsequent takeover of Afghanistan by the Taliban has been the most important geopolitical event since Russia "annexed" Crimea in 2014.
"Current developments are going to have a wide-ranging impact on regional international security," Josep Borrell told the European Parliament on Thursday.
The top EU diplomat said major worries included a possible surge in refugees and increasing complexity in Central Asia.
He voiced concerns that a fresh wave of Afghan migrants might reach Europe, in a replay of the 2015 refugee crisis, when large numbers of people trekked across the continent, many fleeing conflicts in Syria and Iraq.
The 27-nation EU will now have to extend a "diplomatic reach-out" to Iran, Pakistan and India to manage the fallout, Borrell said.
The Taliban's takeover has already left two regional heavyweights Iran and Turkey fearing a refugee influx.
Borrell said the EU is being forced to "establish channels of communication" with the Taliban to ensure the evacuation of the Europeans.
Western countries have been scrambling to airlift their citizens since the Taliban took control of the capital Kabul on Sunday.
"Yes, we have to talk with the Taliban but that doesn't mean recognition."
Unfolding events in Afghanistan culminated in chaotic scenes on Monday when thousands of civilians and diplomats swarmed the Kabul airport, hoping to find seats on departing flights.
The scenes of people plunging to death as they fell off a US military transport plane taking off from the Kabul airport served as a visual confirmation of how the West actually behaves with regard to human rights.
The top EU diplomat expressed concerns that the countries such as China and Russia could be vying to increase their influence in the region following the emerging developments in Afghanistan.
Borrell said he was in touch with NATO Secretary-General Jens Stoltenberg, who will host a virtual crisis meeting of the alliance's foreign ministers on Friday to discuss Afghanistan. Brussels also planned to work with the US and other allies to develop "a common approach".
The West's military engagement in Afghanistan lasted nearly 20 years and cost hundreds of billions of dollars of money, and hundreds of thousands of lives in a bid to drive the Taliban out of power. But as the US and its allies withdrew troops, the Taliban quickly recaptured the country.