In a televised address, Hassan Nasrallah said Syrian refugees should not be coerced into going home, but added that a string of "victories" by President Bashar al-Assad's forces meant it would be safe for many to return.
"Military victories in Syria, the most recent of them the victory in Aleppo... have turned large areas into safe and quiet spaces," Nasrallah said.
He urged "cooperation to return the majority of these refugees to their towns and villages and homes, so they will no longer be refugees sitting in tents or in the streets".
Lebanon hosts around a million registered Syrian refugees and has struggled with the consequences of the war in neighbouring Syria since it began in March 2011.
Hezbollah is a key ally of Assad's government, and its fighters battle alongside his troops against opposition forces, including during the December recapture of second city Aleppo.
Nasrallah said the process of returning Syrian refugees should be "one of persuasion, not of coercion".
"It is the duty of all Lebanese to deal with this issue in a humanitarian fashion, setting aside political considerations or fears," he added.
He also urged the government in Beirut to engage with its Syrian counterpart on the issue, despite the deep antipathy between Lebanese Prime Minister Saad Hariri and Damascus.
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Hariri accused Damascus of involvement in the 2005 assassination of his father, former premier Rafiq al-Hariri, and backed the uprising against Assad.
"Frankly, the Lebanese government must end its obstinacy... and talk to the Syrian government: is this issue not pressing?" Nasrallah asked.
He called on the government to work with Damascus "and develop a single plan, because this cannot be addressed by Lebanon alone, and begging will not solve our problem".
Lebanon has struggled to deal with the massive influx of refugees, who have added to the pressure on its already stretched infrastructure and economy.
Beirut has regularly called for more international assistance, and President Michel Aoun earlier this month urged the international community to facilitate the safe return of refugees.
At the end of January, Syria's Foreign Minister Walid Muallem also "renewed the invitation of the government to Syrian refugees living in neighbouring countries to return".
He "stressed the country was ready to receive them and grant them a dignified life", state news agency SANA reported.
More than half of Syria's population has been displaced internally or externally by the conflict, which has killed more than 310,000 people.
Around 4.9 million people have become refugees.