Demonstrators gathered at the local branch of the powerful UGTT trade union in Kef, 180 km west of Tunis, before marching down the main streets.
"Work, freedom, dignity!" they shouted. "Kef has the right to development!"
They denounced the government over "broken promises" to develop the region.
"This demonstration and strike are important, raising a cry of anger in the face of a situation that cannot last," teacher Rached Salhi said.
Government offices, private companies, shops and cafes were closed and shuttered. Only hospitals, pharmacies and bakeries remained open.
Kamel Saihi, deputy chief of the UGTT's regional office, said governments had marginalised the northeastern region.
"It has been ignored by successive governments since the revolution and (current Prime Minister) Youssef Chahed did the same thing," he said.
Similar protests have rocked other parts of Tunisia in recent weeks, including the southern province of Tataouine and the central region of Kairouan.
The Kef protests were triggered by rumours that a major factory there was set to be relocated to Hammamet, a more developed coastal region.
Six years since a revolution that toppled longtime dictator Zine El Abidine Ben Ali, Tunisia has not been able to resolve the issues that sparked the uprising - including poverty, unemployment and corruption.
Last year saw major protests in the impoverished region of Kasserine following the death of a young person during a demonstration over unemployment.
In October, protesters in the central region of Gafsa shut down two key phosphate mines in a weeks-long dispute over jobs.