The zone in northern parts of Homs province is the third to be established in Syria, which has been ravaged by six years of civil war that have left more than 300,000 people dead.
"From 1200 local time (0900 GMT), units of the moderate opposition and government forces will completely stop firing," Russian defence ministry spokesman Igor Konashenkov said today.
Konashenkov said Moscow and Syrian opposition groups had reached an agreement on the "operational details" of a "de- escalation zone" north of third city Homs at talks in Cairo on July 31.
Under a plan hammered out in May between Russia, Turkey and Iran at peace talks in Kazakhstan, four "de-escalation zones" were to be established across swathes of Syria.
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Last month, Moscow announced the establishment of the first two zones in southern Syria and in the rebel stronghold of Eastern Ghouta near Damascus.
The zone in Homs province is expected to cover towns around Talbisseh, Al-Houla and Rastan.
The fourth zone, in northwestern Idlib province, has yet to be established.
In Talbisseh, shops and vegetable stalls reopened as motorbikes dashed along dust paths between destroyed buildings, an AFP photographer said.
Children ventured out onto the main road and ran into a shop in a market area.
Mustafa Khaled, an activist in the town, told AFP that representatives of Talbisseh, Al-Houla and Rastan were consulted on the deal.
"It is quiet. There have been no violations in the first hour of the agreement," he said today.
Fellow Talbisseh resident Othman Taha said he hoped the ceasefire would hold after years of suffering.
"We hope this is serious," he said.
Al-Houla too was calm, resident Abbas Abu Osama said.
"There had been escalating bombardment of the town with air planes and artillery. But we haven't heard a single gunshot from the checkpoints around us today," he said.
And in Rastan, activist Mohammed Taleb said he welcomed any agreement to end the fighting.
"We in the north of Homs province agree with any deal that stops the bloodshed and destruction," he said.
The Russian defence ministry said Russian military police will set up two checkpoints and three observation posts along the boundaries of the Homs zone on Friday.
Rebels have agreed to "unblock" part of a road running through the safe zone between Homs and the city of Hama further north, spokesman Konashenkov said.
A "Committee for National Justice" made up of rebels and local groups would help oversee the implementation of the plan, he added.
Under a second agreement sealed with rebels in July, Russian forces set up two checkpoints and four observation posts in the rebel enclave of Eastern Ghouta.
Negotiations on the Idlib zone have been complicated by conflicting interests between the international powers and by the presence of large numbers of fighters of former Al-Qaeda affiliate the Fateh al-Sham Front.
Russia is planning a fresh round of talks in the Kazakh capital Astana in late August to thrash out more details of its peace plan.
Separate raids by Russia and the coalition left at least 40 civilians dead on Wednesday, the Observatory said.