The deal, which does not include designated "terrorists" like the Islamic State group, was announced hours earlier by Russian President Vladimir Putin and confirmed by the Syrian army and opposition.
While the truce was standing in most parts of the country early Friday, some fighting broke out near a Christian town in central Hama province with Islamist factions attacking regime forces, according to a monitoring group.
"Fierce clashes took place between the two sides pushing regime forces to withdraw from a hill near Maharda," Abdel Rahman, head of the Britain-based Syrian Observatory for Human Rights, told AFP.
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Key moments in the Syrian conflict
(AFP)
"Small rebel groups and armed loyalists are seeking to destroy the truce because it puts an end to their presence," he said.
Elsewhere, the ceasefire was reported to be holding.
According to an AFP correspondent in Eastern Ghouta, the shelling and airstrikes stopped for more than one hour in the region after intensive shelling and raids on Thursday.
AFP correspondents in Damascus and Idlib said there had been no sound of shelling, airstrikes or clashes since midnight.
The agreement, hailed by Syria's government as a "real opportunity" to find a political solution to the war, comes a week after the regime recaptured second city Aleppo in a major blow to rebel forces.
The deal was brokered by Russia and Turkey, which back opposing sides in the conflict, but does not involve Washington, which has negotiated previous ceasefires with Moscow.
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Syrian youths collect wood from rubble to be used for heating and cooking in the Damascus rebel-held eastern suburb of Zamalka
(AFP)
Putin said Damascus and the "main forces of the armed opposition" had inked a truce and a document expressing a readiness to start peace talks.
Turkish President Recep Tayyip Erdogan described the agreement as a "historic opportunity" to end the Syrian conflict, which has killed more than 310,000 people and forced millions from their homes.
Putin said he would also reduce Moscow's military contingent in Syria, which has been flying a bombing campaign in support of President Bashar al-Assad since last year.
The Kremlin strongman, however, said Russia would continue to fight "terrorism" in Syria and maintain its support for the regime.
Russian Defence Minister Sergei Shoigu said seven opposition groups, including the powerful Ahrar al-Sham, had signed the deal and those who failed to adhere would be considered "terrorists".
Erdogan indicated Turkey would press on with its four-month incursion into Syria against Islamic State group jihadists and Kurdish militia.
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