The first and largest safe zone in northern Syria will include Idlib province and the adjoining districts of Latakia, Aleppo and Hama, the Russian Defence Ministry said.
The broad agreement on de-escalation or safe zones in Syria came into effect at midnight on Friday, the Russian Defence Ministry announced.
The agreement was brokered by Russia, Turkey and Iran on Thursday after a new round of peace talks held in Kazakhstan's capital, Astana. Neither the Syrian regime nor the rebels were direct signatories to the deal, and the opposition's reaction was lukewarm.
The agreement calls for the creation of humanitarian safe zones in opposition-held territory in the northwestern province of Idlib, in parts of Homs province in the centre, in the south, and in the opposition enclave of eastern Ghouta near Damascus.
The fact that the de-escalation agreement was supported by the United Nations, the United States and Saudi Arabia guarantees its implementation, Russian Deputy Defence Minister Alexander Fomin said.
But Syria's leading opposition High Negotiations Committee expressed "concern" about a deal for safe zones, saying it "lacks safeguards and compliance mechanisms."
The de-escalation deal builds on a ceasefire agreed between Russia and Turkey last December that reduced violence for a period but gradually fell apart.
How will the deal look on the ground?
Syrian regime forces and the opposition who have signed onto the deal will agree to halt all hostilities, including the use of warplanes, in the zones.
Several forces have carried out air strikes within Syria, including Russia and a US-led coalition battling Daesh. But a Russian diplomat confirmed on Friday that the terms would prevent the coalition from carrying out strikes in the zones.
The deal calls for "rapid, safe and unhindered humanitarian access" in the areas in question, as well as measures to restore basic infrastructure and allow the "safe and voluntary return" of displaced people and refugees.
Access to the areas will be controlled via security zones complete with checkpoints and observation posts.
The deal calls for security to be "ensured by the forces of the guarantors by consensus," adding that "third parties might be deployed."