"We are very worried for recent developments," Jan Egeland, the head of the UN Humanitarian Taskforce for Syria, told reporters.
A 10-week-old Idlib truce deal hangs in the balance after an alleged chemical attack in the government-held city of Aleppo on Saturday, which triggered retaliatory raids.
The exact circumstances of the attack on three districts of Aleppo remain murky and bitterly disputed.
President Bashar al-Assad's government has blamed fighters in neighbouring Idlib for the attack, which the Syrian Observatory for Human Rights said hospitalised 94 people.
In his final press conference before stepping down on Friday, Egeland stressed that if a chemical attack is confirmed, "it is a war crime."
At the same time, he described the escalation around Idlib, and the first air raids on the area since mid-September, as "very serious."
"Over recent days we have seen provocations and counter-provocations, exchanges of mortars and grenades... We have seen increasing incursions in both directions," he said, warning that "this is the worst possible kind of action in the worst possible place."
"It is really playing with a gigantic powder keg in the middle of three million civilians."
Egeland meanwhile said he was "heartened" that both Turkey and Russia had insisted during Thursday's taskforce meeting that they remained committed to maintaining the U-shaped buffer zone they helped create around Idlib.
During that meeting, representatives of both countries had said "we still believe in this, we are still going to push it," Egeland told reporters.
He applauded both for their efforts but said they could do more to ward off catastrophe in Idlib.
He urged Turkey to "curb the bad tendencies among armed opposition groups", and said "certainly Russia can cease air raids immediately, and that is what they need to do."
His comments came as negotiators from Iran, Russia and Turkey concluded a meeting in Kazakhstan's capital Astana in a bid to preserve the Idlib truce.
Egeland acknowledged that it was difficult to leave a post he has held for more than three years, because Syria's grinding civil war, which has killed more than 360,000 people and displaced millions, "is not over."
He said he was proud of the work of the taskforce, which was set up in early 2016 as a place where the United States, Russia and other countries could negotiate access for desperately-needed aid and civilian protection.
But while he hailed the feat of providing aid to millions of people each month, he acknowledged that "we failed on the protection side."
Humanitarians, he said, had "ended up as impotent witnesses to the violence."
