Jordan's King Abdullah II suggested that failing to come together would leave the region open to outside influence.
A show of unity was expected on the Israeli-Palestinian question, but on other issues analysts said any breakthrough was highly unlikely.
As the summit of the 22-member Arab League opened in Sweimeh on the Dead Sea coast, Jordan's King Abdullah II suggested that failing to come together would leave the region open to outside influence.
"We need to take the initiative to find solutions to all the challenges we face in order to avoid foreign interference in our affairs," he said.
Arab leaders have been unable to find common ground on how to end Syria's conflict, which in six years has left more than 320,000 dead and forced millions from their homes.
Various Arab nations are supporting different proxy forces on the ground and there is disagreement on the future of President Bashar al-Assad, whose participation in the league has been suspended since 2011.
While some say Assad must go for any peace deal others, including Egypt's President Abdel Fattah al-Sisi, have not insisted on his departure as a condition for a political agreement.
Arab divisions have allowed other nations including Iran, Russia and Turkey to take the diplomatic initiative on Syria.
Visiting a refugee camp in Jordan on Tuesday before attending the summit, UN Secretary General Antonio Guterres echoed calls for differences to be set aside.
"Arab unity is a very important element in order to allow this region to be stabilised and for... the Syrian refugees to find again a future that corresponds to their aspirations," he said.
Talks are expected on a range of other issues including efforts against the Islamic State group, the war in Yemen, continued unrest in Libya and the Israeli-Palestinian conflict.
On the Palestinian question, the leaders are set to oppose plans by US President Donald Trump to move Washington's embassy in Israel to Jerusalem and consider alternatives to a Palestinian state.
A draft summit statement, drawn up by the Palestinian delegation and obtained by AFP, says the league's members "reaffirm their commitment to the two-state solution".
It calls on "all countries to respect UN Security Council resolutions that reject Israel's annexation of occupied east Jerusalem" and "not to move their embassies" from Tel Aviv to the Holy City.
Since taking office in January, Trump has indicated he is willing to break with decades of US policy by moving the embassy and being open to a one-state solution to the Israeli-Palestinian conflict if both sides agree.
Palestinian president Mahmud Abbas met late Tuesday on the sidelines of the summit with Trump adviser Jason Greenblatt, who said on Twitter that it was a "very positive meeting" with "discussion on how to make tangible progress on peace".
Abbas is expected to visit the White House next month, after a visit by Sisi scheduled for April 3. Abdullah is also expected in Washington soon.
Jordanian officials have stressed fighting "terrorism" as a major theme of the summit, in particular the threat from IS which is facing US-backed offensives in Iraq and Syria.
"Arab and Muslim countries must unite their efforts to combat terrorism," Abdullah said in his address.
On Yemen, regional powerhouse Saudi Arabia will be looking for more support for the coalition it launched two years ago to intervene in support of government forces against Iran-backed Shiite rebels.
The Huthi rebels have seized control of large parts of the Arabian Peninsula nation. Continued fighting has left several thousand dead and raised fears of famine.
Riyadh has been frustrated by a lack of willingness by some Arab nations to back the coalition, in particular from key military power Egypt.
The Saudis cut off oil shipments to Egypt in October, apparently in connection with disagreements on Yemen and Syria, though the shipments resumed earlier this month.
Previous Arab League summits have seen little progress in overcoming divisions and analysts were expecting more of the same.
"I think this summit won't be any different," said Oraib al-Rantawi, head of the Al-Quds Centre for Political Studies.
"The Arab (political) system is weak, divided and has been plagued by defects for years," he said. "No breakthrough is expected."
Also in attendance was Sudan's President Omar al-Bashir, who is wanted by the Hague-based International Criminal Court for alleged genocide and war crimes related to the conflict in war-torn Darfur.