BUS Éireann, the Republic's state-owned bus company, is to suspend indefinitely its Dublin-Belfast service due to financial pressures as a result of the Covid-19 pandemic.
Its buses will be withdrawn from the X1 cross-border route in the coming months.
Translink, the north's public transport operator, said it remains committed to operating the route and will work with transport officials to ensure a continuity of services.
"We will communicate any changes on the timetable and work to minimise the overall impact on our passengers," a spokeswoman said.
Bus Éireann also announced its Expressway services from Dublin to Cork, Galway and Limerick are to cease.
No cessation dates have been decided, but changes are likely to start early next year.
The board of Bus Éireann said it made the decision in order to protect other core routes amid the "challenges posed by Covid-19".
It said the service cuts will not result in any job losses as drivers are needed for other routes.
Bus Éireann said the X1 service from Dublin to Belfast and X51 from Galway to Limerick have not been in receipt of emergency funding, and services will formally cease on these routes over the next few months.
The south's National Transport Authority will review requirements along these routes to mitigate any impact, it added.
Bus Éireann chief executive Stephen Kent said continuing to operate the Expressway routes would "incur unsustainable losses" and withdrawing them would "thereby avoid job losses in a very difficult trading environment".
A Translink spokeswoman said in a statement: "Due to the ongoing challenges and impact of Covid-19, Bus Éireann, our current partner on the X1 cross-border Belfast to Dublin route, have taken the difficult decision to suspend their service indefinitely following a review and an analysis over the past number of months.
"This move by Bus Éireann will be introduced formally over the coming months.
"Translink remain committed to operating this route and will work with Bus Éireann to manage the transitional period in order to maintain services for passengers along this corridor.
"We will communicate any changes on the timetable and work to minimise the overall impact on our passengers.
"We will be working closely with both the Department for Infrastructure and the National Transport Authority in the south to ensure continuity of services in the future and as we 'build back responsibly' from this pandemic."
Private bus company Aircoach is continuing to operate on a reduced timetable its service for Dublin City to Belfast via Dublin Airport.
Dermot O'Leary, general secretary of the National Bus and Rail Union, expressed disappointment with Bus Éireann's decision and urged politicians to "step up to the plate and protect the services".
He told RTÉ: "Without Bus Éireann during the Covid crisis, there would have been no bus service, essential workers could not have gone into hospitals, doctor's surgeries, pharmacies."
Stormont's Department for Infrastructure said the minister Nichola Mallon is "committed to securing island wide services between Belfast and Dublin and is concerned by this news".
"The Department for Infrastructure will continue to work to provide services for our communities north-south," a spokeswoman added.
