Journalists on the front line saw at least 15 vehicles carrying men, women and children leaving Baghuz.
The US-backed Syrian Democratic Forces (SDF) alliance, which is besieging the area, said it did not yet know if any IS fighters were among the passengers.
However, a UK-based monitoring group said it believed all the civilians and militants who were in Baghuz had left.
The Syrian Observatory for Human Rights cited its sources as saying the militants had agreed to surrender following extensive negotiations with SDF.
On Tuesday, the UN expressed concern about the fate of some 200 families reportedly trapped in Baghuz.
Human rights chief Michelle Bachelet said they were apparently being actively prevented from leaving by IS and continued to be subjected to intense bombardment by SDF and US-led coalition forces.
A convoy of about 50 lorries arrived on the outskirts of Baghuz after Ms Bachelet spoke. But none of them had departed by nightfall, Reuters news agency said.
US-led coalition aircraft reportedly carried out two strikes in the area before the first lorries left on Wednesday.
“We have special forces working on the evacuation of civilians. After many days of trying, we were able to evacuate the first batch today,” SDF spokesman Mustafa Bali told AFP news agency.