In a statement on Twitter, Riad Hijab said he was stepping down after nearly two years serving as the head of the Syrian opposition's High Negotiations Committee.
"I find myself today forced to announce my resignation from the High Negotiations Committee, wishing them further achievements, and wishing for my beloved country Syria peace, security, and stability," he wrote in Arabic.
Hijab was serving as Syria's prime minister when he defected in 2012, and took charge of the opposition HNC when it was formed in December 2015 in Saudi Arabia.
He did not provide specific reasons for his resignation but said he had faced "attempts to lower the ceiling of the revolution and prolong the regime of (Syrian President) Bashar al-Assad."
Immediately after Hijab's resignation, several other HNC officials including Suheir Atassi and Riad Naassan Agha also announced they were withdrawing from the body.
The resignations come just two days before opposition figures are to gather in Riyadh, at the invitation of the Saudi foreign ministry, to prepare for UN-led peace talks later this month.
Opposition figures and analysts suspected that hard-line regime opponents like Hijab would be side-lined in that summit.
"With his resignation, Hijab pre-empted the Riyadh conference on Wednesday, which was planning to form a (new) HNC, elect a new head coordinator, and form a delegation to Geneva talks," a senior opposition official told AFP, speaking on condition of anonymity.
||The Riyadh summit will aim to unite representatives of the HNC, the Istanbul-based National Coalition prominent opposition grouping, independent opposition figures, and members of two groups known as the Cairo and Moscow platforms
Russia's foreign minister welcomed the resignations, saying it will pave way for "realistic" dialogue between the regime and the opposition.
"The retreat of radically minded opposition figures from playing the main role will make it possible to unite this motley opposition - internal and external - on a more reasonable, realistic and constructive platform," Sergei Lavrov said.
"We will support the efforts made by Saudi Arabia in this respect."
Attempt at unity
The Riyadh summit will aim to unite representatives of the HNC, the Istanbul-based National Coalition prominent opposition grouping, independent opposition figures, and members of two groups known as the Cairo and Moscow platforms and seen as more favourable to the regime.
The United Nations' special envoy to the Syrian crisis, Staffan de Mistura, has intensified his calls in recent months to unite the various bodies into a single opposition group.
Syrian government officials had long complained they wanted to deal with one, unified delegation at peace talks.
But a senior HNC official told AFP on Monday that "uniting opposition groups will be a difficult task in light of differences in opinion, particularly on Assad's fate."
Since the uprising against Assad erupted in 2011, Syria's political and armed opposition has suffered internal fragmentation.
The Syrian conflict began when the Baath regime, in power since 1963 and led by President Bashar al-Assad, responded with military force to peaceful protests demanding democratic reforms during the Arab Spring wave of uprisings, triggering an armed rebellion fueled by mass defections from the Syrian army.
Hundreds of thousands of civilians have been killed in the war, most of whom at the hands of the regime and its powerful allies, and millions have been displaced both inside and outside of Syria.
The brutal tactics pursued by the regime, which have included the use of chemical weapons, sieges, mass executions and torture against civilians have led to war crimes investigations.
||Hijab's resignation comes amid intense violence in Damascus suburbs and the capital, which continued for days despite a truce brokered between the government and armed rebels there by Russia, Turkey and Iran
Hijab's resignation comes amid intense violence in Damascus suburbs and the capital, which continued for days despite a truce brokered between the government and armed rebels there by Russia, Turkey and Iran. The week-long fighting has claimed dozens of lives, as government forces conducted airstrikes and shelling on the besieged eastern Ghouta suburb of Damascus. Rebels responded with shells, and a group of insurgents attacked a military base.
On Monday, the Britain-based Syrian Observatory and the Ghouta Media center said they documented the death of a woman and four children in Kfar Batna village in the rebel-held eastern suburb.
Eastern Ghouta suburbs have been largely under a tight blockade by pro-government forces, despite the August “de-escalation” agreement that was supposed to allow in humanitarian aid. The UN estimates there are around 350,000 people trapped by the blockade. The recent fighting as killed at least 87 civilians in the suburbs, according to the Observatory.
Also on Monday, the state news agency SANA said two Judo players were killed and more than 12 other players were injured, some critically, when a rebel-lobbed mortar round hit a sports hall they were training inside it in Damascus. The agency earlier reported six people were killed, including a child, when shells hit two Damascus neighbourhoods.