"They should leave. We have had enough," an inhabitant of Yannitsa told the Skai broadcasting group as several dozen people tried to prevent the dawn arrival of 60 asylum-seekers from the islands of Lesbos and Samos.
Around 60 other migrants have already been relocated to Yannitsa and "we have had many problems," the local resident said, Presstv Reported.
The migrants finally managed to leave their bus as police looked on, and occupy rooms at hotels in the town.
To the east in Serres, another protest was held against the arrival of around 20 migrants.
Over the weekend, roughly 900 people were transferred from Greek islands to sites on the mainland, and the government has said it wants to relocate 20,000 by the end of the year.
Ten days ago, inhabitants of Nea Vrasna prevented 380 asylum-seekers from reaching hotels by stoning their buses, which turned around and headed to another relocation site in central Greece.
The country has again become a key point of entry for migrants to Europe, possibly owing to a new policy from neighboring Turkey, which threatened in September to ease border controls if it did not receive more international aid.
In the past four months, "40,000 migrants and refugees have arrived," junior minister Georges Koumoutsakos told Skai in an interview.
"We have to show solidarity with border regions that have borne the brunt" of the influx, he added.
Greek figures show that more than 34,000 people now live in miserable conditions on five islands that in theory can host 6,300 while they register as asylum-seekers.
On Friday, lawmakers approved a law that tightens asylum procedures and is aimed at easing "a state of prolonged paralysis," according to conservative Prime Minister Kyriakos Mitsotakis, who said the country was trying to clear nearly 70,000 pending requests.
He accused Turkey and the previous center-left Greek government for the spike in migrant arrivals.