Britain's "firm preference" is to negotiate a Northern Ireland Protocol deal with Brussels rather than tear up the Brexit treaty that created the Irish Sea border, Liz Truss said.
The Foreign Secretary stressed the UK was "open" for more talks but warned that problems were "baked into" the Protocol, which she said needed substantial renegotiation.
"It does not mean ripping up the Protocol, but it does mean changes to the Protocol itself," Ms Truss said before meeting with business leaders in Belfast to discuss the talks over the agreement.
The EU insists it will not enter into a wholesale renegotiation of the Protocol but will discuss ways of improving its working within the framework of the existing treaty.
Brussels has rejected Ms Truss' demand that European Commission Vice-President Maros Sefcovic be given a new negotiating mandate to make wholesale changes to the Protocol.
Ms Truss said, "The problems of the Protocol are baked into the existing legal text. Without changes to this mandate, we cannot fix the problems."
Writing in the Irish Times, Ms Truss struck a more conciliatory tone after US accusations that threats to unilaterally override the Protocol endangered the Good Friday Agreement.
"Our firm preference is to reach a negotiated solution," Ms Truss said, "While our door remains open to talks, we cannot allow any more drift or delay."
But she doubled down on British claims the Protocol was putting the peace process at risk because it had lost the consent of unionists.
"It is clear that these problems are putting the Belfast Agreement under strain," she said. "After 18 months of trying to make it work, it is clear the current arrangements are not sustainable."
She said the 2019 Brexit agreement, which introduced border checks on British goods entering Northern Ireland, was the "biggest obstacle" to the restoration of power-sharing in Stormont.
The DUP, which lost its majority to Sinn Fein for the first time in May 5 elections, has blocked a new Northern Ireland Executive until the Protocol is removed or replaced.
Ms Truss claimed planned legislation to override parts of the treaty would protect the Good Friday accords and help convince the DUP to join a new Northern Ireland Assembly.
"The UK has a duty to take the necessary decisions to preserve peace and stability," Ms Truss said.
The EU warns the bill or the use of Article 16 of the Protocol to override parts of the agreement would break international law and risk a trade war with Brussels.
The UK argues the Protocol is having a chilling effect on trade with Northern Ireland because of the new checks and red tape to ensure British goods entering the province meet EU standards.
Northern Ireland continues to follow about 300 EU rules to prevent the need for a hard land border with EU member Ireland, which could inflame tensions on the island.
Ms Truss said implementing the Protocol in full, which has still not happened despite the treaty coming into force at the end of 2020, would pose an "existential" threat to businesses struggling with extra costs and paperwork.
The UK wants a "green channel" with no checks for all British goods destined for Northern Ireland only . A red channel for goods at risk of crossing the invisible border into the EU's Single Market would have checks to make sure they meet EU standards.
This would be backed by a trusted trader scheme and "robust enforcement", Ms Truss said. The scheme would give the EU real time commercial data on trade flows but Brussels wants the information to be state data rather than from businesses.
Ms Truss said the Protocol in its current form made it impossible to allow businesses in Northern Ireland to choose whether to follow EU or UK regulations. Under the treaty, which gives the province unique dual access to both markets, they must follow EU rules.
The agreement also means Northern Ireland must follow EU rules on subsidies, as well as animal and plant health regulations. Ms Truss said it prevented a whole of UK "tax and spend policy."
In October, The EU offered a series of border check cuts in return for bolstered market surveillance to make sure goods were not crossing into Ireland.
Brussels accuses the UK of failing to engage with those proposals, which included changing EU law to ensure the supply of cheaper NHS drugs to Northern Ireland.
Instead the Commission will see the UK demands to radically overhaul the Protocol, which Brussels has ruled out, as a return to its initial negotiating position set out in June.
On a trip to Dublin on Tuesday, Senior US Democrat Richard Neal accused London of "vagueness" over why it planned to override the Protocol and suggested the dispute was a "manufactured issue".
Mr Neal has warned Congress will block a UK-EU trade deal if unilateral action is taken and said it was now "up to London" to find a solution.
DUP leader Sir Jeffrey Donaldson said ignoring unionist opposition to the Protocol exposed the Congressman's "ignorance and prejudice and slavish adherence to Sinn Fein dogma."
In London on Tuesday, Sinn Fein told Conservatives to stop using the Protocol to distract from Boris Johnson's domestic problems with Partygate,
Security has been stepped up for Mr Neal's visit to Northern Ireland after details of his itinerary reportedly leaked to loyalist paramilitaries.