Israeli Prime Minister Benjamin Netanyahu's vow to never evacuate Jewish settlements from occupied land has drawn outrage from Palestinians.
The pledge has also complicated matters for the Trump administration's would-be peace envoys as they try to restart talks.
The Palestinians called on the White House to intervene, and visiting UN Secretary-General Antonio Guterres challenged Mr Netanyahu's comments, reiterating the international community's opposition to Israeli settlements.
More than 100 settlements dot the West Bank and a string of US-led peace plans over the past two decades have called for evacuating at least some of them to make way for the establishment of an independent Palestinian state alongside Israel.
Mr Netanyahu's hard-line religious and nationalist base opposes such a move.
Mr Netanyahu appears to have been emboldened by the election of President Donald Trump who, unlike a string of predecessors, has not endorsed the idea of a two-state solution.
Mr Trump also has surrounded himself with a team of advisers who are long-standing supporters of settlements. These include his son-in-law, Jared Kushner, who is leading the peace efforts and was in the region last week for meetings with the sides.
Mr Netanyahu spoke at a ceremony on Monday night in Barkan, a settlement in the northern West Bank.
"There is a momentum of development in Judea and Samaria," he said, referring to the West Bank by its biblical name.
"We have returned here for eternity," Mr Netanyahu added. "There will be no more uprooting of settlements in the Land of Israel. Settlements will not be uprooted."
The Palestinians seek all of the West Bank, along with east Jerusalem and the Gaza Strip, for an independent state alongside Israel.
Israel captured the areas in the 1967 war, though it withdrew from Gaza in 2005.
The Palestinians say that settlements on occupied lands are illegal and undermine the goal of a two-state solution by gobbling up territory they seek - a position that is widely backed by the international community. More than 600,000 Israeli Jews now live in the West Bank and east Jerusalem.
While Mr Netanyahu has made similar pledges before, the timing - on the heels of Mr Kushner's visit and with the UN chief in town - gave it added significance and raised questions about his intentions for resolving the conflict with the Palestinians.
During the Obama administration, Mr Netanyahu paid lip service to the idea of a two-state solution, implying that a Palestinian state could be established in parts of the West Bank or that settlements might somehow remain behind in a future Palestine.
Now, with Mr Netanyahu avoiding talk of Palestinian independence or a territorial withdrawal, the Palestinians are pushing the new US administration to take a stand.
In particular, they have been pressing Washington to call for a freeze on settlement construction and to endorse the two-state solution.
Nabil Abu Rdeneh, spokesman for Palestinian President Mahmoud Abbas, denounced Mr Netanyahu's comments and said they hinder US peace efforts.
"This is an Israeli message to the US administration," he said. "We call upon the US administration to deal with these provocations," which, he said, hinder US peace efforts and are "an attempt to return things to square one".
The Palestinians have expressed impatience with Mr Kushner's slow start. Mr Kushner held talks last week with Israeli and Palestinian leaders, as well as separate meetings with Arab allies in Egypt and the Gulf.
The Americans appear to be seeking a broader region-wide approach to peace by bringing in moderate Arab countries.
A senior White House official played down Mr Netanyahu's comments.
The official said the Israeli position was known and that the US is talking to all sides to reach a deal "that factors in all substantive issues".