More than 1,000 European parliamentarians from across political lines strongly opposed Israel's plan to annex parts of the West Bank in a letter published on Wednesday.
The lawmakers express "serious concerns" about the US plan to end the Israel-Palestinian conflict which would allow Israel to annex 30 per cent of the West Bank territory.
"We are deeply worried about the precedent this would set for international relations at large," the letter states, warning of the "commensurate consequences" such a move could spark.
"We are profoundly concerned about the impact of annexation on the lives of Israelis and Palestinians, as well as its destabilising potential in a region on our continent's doorstep.
"Europe must take the lead in bringing international actors together to prevent annexation and to safeguard the prospects of the two-state solution and a just resolution to the conflict," it adds.
The letter, signed by 1,080 European parliamentarians from 25 countries, was initiated by four prominent Israeli figures, including Avraham Burg, a former Speaker of the Knesset, and Michael Ben-Yair, a former Attorney General of Israel.
They argue the Vision for Peace plan presented by the US administration of President Donald Trump "departs from internationally agreed parameters and principles".
"It promotes effectively permanent Israeli control over a fragmented Palestinian territory, leaving Palestinians with no sovereignty and giving a green light to Israel to unilaterally annex significant parts of the West Bank," they went on.
Israeli Prime Minister Benjamin Netanyahu has said annexation would be put to a vote on July 1.
Trump's peace plan has been heavily criticised for being overly Israel-friendly — the Palestinian Authority boycotted the talks.
Under the plan, a future Palestinian state would be smaller than previously imagined with several parts disconnected from one another. It also narrows the definition of what constitutes a "Palestinian refugee" — thus reducing access to aid — and bars a future Palestinian state from having security forces.
The letter's signatories noted that the EU's top diplomat, Josep Borrell, has said that Israeli annexation of West Bank territory "could not pass unchallenged" and warned that "failure to adequately respond would encourage other states with territorial claims to disregard basic principles of international law".
Their appeal comes a day after more than 100 EU and Israeli lawmakers sent a letter to Borrell urging him to "renew the work of the EU-Israel Association Council and resume its activities with regular meetings as soon as possible".
The council has not met since 2012 due to disagreements over the peace process.