Police said no injuries were reported from Monday’s protest and that the fire was believed to have been set deliberately at the Moria camp, made up of makeshift homes housing over 1,000 refugees.
Some of the refugees who live there reportedly held a protest saying their applications were not being processed.
According to police, a small group was involved in the protest at the camp, a large area of trailers and tents surrounded by razor wire fences.
Police had allegedly been called to the camp before the fire broke out to respond to a “major disturbance.”
Videos showed a large plume of black smoke billowing from inside the Moria camp.
Outside the camp, there were scenes of panic and chaos as families escaped the plume of smoke and fire trucks sped along to tackle the fire.
More than 60,000 refugees remain stranded in Greece awaiting relocation to other European countries. About 14,000 of them are stuck on Lesbos and other Greek islands near Turkey.
They are not allowed to travel to the Greek mainland under the terms of an agreement between the European Union and Turkey reached last year.