In dramatic scenes overnight, the migrants at Moria refugee camp fled fires that broke out at multiple points and gutted much of the camp and surrounding hillside olive groves.
Protests also broke out involving migrants, riot police and firefighters.
“It has been a very difficult night,” government spokesman Stelios Petsas said, adding that a state of emergency would be declared later on the island.
Some 12,500 people were living at the Moria camp and the surrounding area, where additional restrictions have been imposed over the past week after a Somali resident tested positive for coronavirus.
There were no reports of injuries.
The fires broke out overnight, police and fire officials on the island told the Associated Press, adding the cause of the blazes, as well as the full extent of the damage, remained unclear.
They did not confirm local reports that the fires had been set deliberately in protest at the lockdown measures but said firefighters had “met resistance” from some camp residents.
Mr Petsas said that arson was being considered as a possible cause of the fire.
Before dawn, riot police set up cordons along a road near the camp to restrict the movements of migrants.
Health authorities on Tuesday said 35 people at the camp had been confirmed infected with the virus so far after a major testing drive was ordered at the overcrowded facility.
Those with confirmed infections were being kept in isolation at a separate site that was not affected by the fire, officials said.
Lesbos was Europe’s busiest crossing point in 2015-16 for illegal migration during a massive westward movement of refugees, many fleeing war in Syria and Iraq and travelling through Turkey.
After that wave of migration, Greece set up camps on Lesbos and four other islands, helped with European Union funding, and more recently also set up a network of camps on the mainland.
Firefighters on Lesbos were also battling two other forest fires in the west of the island.
