The pope said he was "profoundly concerned" about recent developments regarding Jerusalem, which he called a "special vocation for peace" and a sacred place for Christians, Jews and Muslims.
"I pray to the Lord that its identity is preserved and strengthened for the benefit of the Holy Land, the Middle East and the whole world and that wisdom and prudence prevail to prevent new elements of tension from being added to a global context already convulsed by so many cruel conflicts", he said.
Pope Francis made foreign politics the focus of his weekly general audience, pinpointing the highlights of his recent trip to Myanmar and Bangladesh and calling on the worldwide community not to destabilize the current situation in Jerusalem.
Palestinians and Arab leaders have warned the move is a threat to the Middle East peace process.
As part of the plan, the Trump administration is expected to eventually move the USA embassy from Tel Aviv to Jerusalem, and while Israel welcomes the changes, both Palestinians and Arab leaders have voiced concern that the move could jeopardize the peace process in the Middle East, according to the BBC.
"I would like to make a heartfelt appeal for everyone's commitment to respect the city's status, in conformity with the pertinent United Nations Resolutions", he said, as quoted by the Vatican Radio, an official broadcaster.
Papal appeal comes shortly after news came out that President Trump would be recognizing Jerusalem as the capital of Israel.
Before making his public comments, Francis met privately with a group of Palestinians involved in inter-religious dialogue with the Vatican.
He spoke of dialogue between religions "and also in civil society".
The change is a recognition of "reality", officials said, both the historic reality that Jerusalem has been the capital of the Jewish nation since ancient times and the modern reality that the city is the seat of Israel's government, housing its legislature, supreme court, prime minister, and executive agencies.
The Vatican supports a two-state solution.
The Vatican signed its first treaty with the "State of Palestine" the following year.