Local Media said around 50 people returned to Syria's Moadamiyat al-Sham through the Masnaa border crossing.
They left in three buses brought from Syria in addition to a number of private cars.
The representatives of senior Syrian general Maher al-Assad, the U.N. and the Syrian Arab Red Crescent accompanied the refugees home.
Mohammed Nakhla, 58, was anxious to set foot in his home country for the first time in six years.
"I've never felt better," he said, as he waited to return with 10 family members to Moadamiyet al-Sham.
Damascus has approved the return of 450 Syrian refugees from Lebanon from a list of 3,000 requesting to do so, Lebanon's state news agency NNA said this week.
Lebanon hosts just under one million registered refugees from the conflict in neighboring Syria, although authorities say the real number is much higher.
As some battlefronts in Syria's devastating seven-year war have quietened, Lebanese officials are ramping up demands that refugees go home.
On Thursday, several hundred Syrian refugees left the Lebanese border town of Arsal, returning to their hometowns around Damascus.
The operation was also coordinated between Lebanon's General Security and Syrian authorities.
On Friday, the head of Lebanon's Hizbullah, Sayyed Hassan Nasrallah, said his powerful movement was creating a mechanism to help Syrian refugees return home, in coordination with Lebanese authorities and Damascus.
Nasrallah said the group was setting up centers with phone numbers and social media accounts where refugees could sign up to return home.
Earlier this year, around 500 refugees also left southern Lebanon for Syria in a return organized by Beirut and Damascus.
Several thousand have independently left in recent years.