The shock IS advance on two rebel-held towns came as the jihadist group is facing an offensive further east in its own heartland of Raqa province.
IS fighters cut a key road between the rebel towns of Azaz, close to the Turkish border, and nearby Marea, journalist Maamoun Khateeb told AFP from Azaz.
"This is a disaster," Khateeb said, adding that some 15,000 people were now besieged in Marea.
The jihadist onslaught threatens tens of thousands of internally displaced Syrians living in informal camps near the border, closed by Turkey for several months.
"We are terribly concerned... about the estimated 100,000 people trapped between the Turkish border and active front lines," said Pablo Marco, regional operations manager for Doctors Without Borders (MSF).
MSF said it was evacuating patients and staff from a hospital it supports in Salamah, a nearby town, just three kilometres (two miles) from the front line.
"There is nowhere for people to flee to as the fighting gets closer," Marco said.
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Gerry Simpson from Human Rights Watch said the number of Syrians trapped along the closed border could be as high as 165,000.
Marea and Azaz both fell to opposition forces in 2012 and have been vital stops along a rebel supply route from Turkey.
IS has tried to advance on both towns for months.
In a statement on Friday, the jihadist group said it launched a "surprise attack" and seized a series of villages near Azaz.
Also on Friday, government bombardment on rebel-controlled areas of Aleppo province left at least 15 people dead, rescue workers told AFP.
At least two people were killed in barrel bomb attacks on an opposition-controlled eastern district of Aleppo city, the civil defence -- known as the White Helmets -- said.
Air strikes also killed nine people in the town of Hreitan and four in Kfar Hamra.
Since fighting intensified there in 2012, Aleppo province has been transformed into a patchwork of territories held by the government, rebels, Kurds, and jihadists.