Pendyffryn Medical Group in Prestatyn, Denbighshire, claims it cannot recruit enough doctors to continue the service.
Doctors at the practice said they had no choice but to tender their resignation after "practically begging GPs" to join.
Betsi Cadwaladr health board said it was working closely with the practice.
Dr Eamonn Jessup, who works at the practice, said: "We can't find anyone. We keep advertising, we've been desperate to find doctors. We've been practically begging GPs to come to us.
"We've also got the perfect staff, the perfect nursing team - there are just no doctors."
Dr Jessop, who is chairman of the North Wales Local Medical Committee, said there were currently five whole-time equivalent doctors at the practice, but that was due to drop to three in the coming months.
He said the practice had seen waiting times creep "up and up and up" as efforts to recruit more staff failed.
A new way of providing primary health care would exist from 1 April, he added, saying doctors were willing to work with the health board over the transition period.
Ann Jones, Labour AM for the Vale of Clwyd, called it "a blow" to primary care delivery in the area.
A joint statement from the practice and the health board said the contract would end on 31 March 2016.
"From April 2016, the Pendyffryn Medical Group partnership will no longer be the provider of GP and primary care services," the statement read.
"The health board is responsible for making sure that people in north Wales have access to these services. It is therefore working closely with Pendyffryn Medical Practice to plan how their patients will continue to get the local services that they need from April 2016 onwards.
"Over the next six months, we will keep patients and other members of the local population informed of our progress, and will respond to any concerns and questions.
"We will also work together to support all the staff in the practice and ensure that they are kept up-to-date and understand the new arrangements that are being put in place."
A GP practice which has more than 18,000 patients on its books is terminating its contract with the health board over recruitment issues.