NATO head Anders Fogh Rasmussen said on arriving for the talks.
"We cannot ignore the risks of regional spillover, with (the) possible implications for Allied security," Rasmussen said.
Earlier this year NATO deployed Patriot anti-missile batteries along member Turkey's border with Syria after several villages were hit by artillery fire.
"We must continue to remain vigilant," Rasmussen said.
The one-day meeting at NATO's Brussels headquarters comes as President Bashar al-Assad appears to have made headway against the rebels - and after Iran, his close ally, said it wanted him to stay on and contest elections in 2013.
On Sunday, Kerry announced a doubling to $250 million of aid and non-lethal equipment for the rebels in Syria.
He urged other countries to follow suit amid sharp differences over the wisdom of providing arms, especially given the links some Syrian opposition groups have with Al-Qaeda.
"This conflict is now spilling across borders and is now threatening neighbouring countries," Kerry said after the announcement in Istanbul. "This bloodshed needs to stop."
Afghanistan is the other main talking point on Tuesday as ministers prepare for the end of NATO's combat mission and its post-2014 training role.
This year is crucial as Afghan forces take on the lead security role from NATO, a "milestone" in Rasmussen's words.
Kerry is to hold a meeting in Brussels on Wednesday with Afghan President Hamid Karzai, the head of Pakistan's armed forces, Ashfaq Kayani and other top Pakistani officials.
"This is a critical year in Afghanistan," Kerry said on Monday, referring to the security handover.
The aim, he said was to "talk about how we can advance this process in the simplest, most cooperative, most cogent way so that we wind up with both Pakistan's and Afghanistan's interests being satisfied, but most importantly, with a stable and peaceful Afghanistan."
Relations between Islamabad and Kabul have been strained for many years and Karzai has accused Pakistan of aiding the Taliban, who seek refuge along their rugged border.
"We need the positive engagement of Afghanistan's neighbours, including Pakistan," Rasmussen said.
After withdrawal in 2014, NATO plans to post between 8,000 and 12,000 troops to train and advise Afghan forces but the terms for their presence have not yet been agreed with Kabul.
Rasmussen said he expected to meet Karzai on Tuesday but this would on an individual basis.
Russia also figures largely at the talks, with a session of the NATO-Russia council attended by Foreign Minister Sergei Lavrov devoted to a review of ties, including the Middle East.
Russia is a longstanding ally of President Assad's and also plays an important role in Afghanistan, where it helps with logistics and provides helicopters and training for Kabul.
Kerry is due to meet Lavrov separately for talks which a senior NATO diplomat said were hoped to boost US-Russia ties and lead to "intensified dialogue" with the alliance as a whole.