Almost 7,000 patients across Belfast are caught up in the latest crisis to hit the health service in Northern Ireland.
Ravenbank Surgery in east Belfast has announced it will close at the end of March, while a second practice in north Belfast is also facing closure.
It comes after efforts to find doctors willing to take over running of both surgeries have failed and highlights the impact the GP shortage is having on patient care in Northern Ireland.
GPs working at Antrim Road Medical Centre, which is facing collapse after a colleague retired, have blamed the situation on "the persisting crisis in the NHS", which they said "has had a huge impact on general practice".
In a statement posted on the surgery website, they said: "With an ageing population and the complex medical needs of patients rising, we have seen a significant increase in the demands on GP surgeries.
"We have also seen a large number of GPs retiring from the profession and a huge decrease in the number of GPs willing to take on partnership positions in practice.
"We have advertised for new partners since Dr Peter retired in 2016 without success. Therefore, this situation has unfortunately led to Dr Michael and Dr Nuala making the decision to transfer the responsibility of managing the practice to the Health Board in an attempt to try and find a solution."
The Health and Social Care Board now has six months to find a doctor to take on the contract to run the surgery.
If this is unsuccessful, the surgery may have to close and patients will be subsumed into surrounding practices.
However, this would increase the workload on already overstretched family doctors and one GP has warned this is a "far from ideal solution".
"Until now, the shortage of GPs has really impacted on rural areas, but we're now seeing it happening in Belfast, which is worrying," he said.
"It shows that everything is not rosy in the garden of general practice.
"A lot of good work has been done to try and address the issues being experienced by GPs but, at the end of the day, if you don't have enough GPs, the whole thing falls apart."
The Royal College of GPs in Northern Ireland (RCGPNI) expressed alarm at the imminent closure of Ravenbank Surgery and the threat to the future of Antrim Road Medical Centre.
Dr Laurence Dorman, RCGPNI chair, said: "The closure of these two respected Belfast practices would be terrible news for GPs, practice teams and their patients.
"Unfortunately, they are not surprising.
"Between 2014 and 2019, 23 other GP practices have closed across Northern Ireland and we know there is a risk of more closures this financial year.
"In recent months we have spoken to health leaders about how difficult it is to run a practice.
"GPs and our teams are working to our absolute limits to provide safe, high-quality care, while under intense pressure.
"When a practice closes for whatever reason it is incredibly difficult for everyone involved - especially patients.
"Generations of institutional knowledge about patients and their families can be lost and there also follows a ripple effect, where neighbouring practices become at risk of destabilisation."
Dr Dorman said, with the return of Stormont, reform of the health service must be a priority.
He also called for urgent investment in the GP workforce and premises, as well as strategies to address the unsustainable workload and pressures being endured by family doctors and their staff.
The HSCB did not provide a comment.