The Shiite movement, which Washington considers a terrorist organization, was "providing every possible and necessary aid to help the Syrian army" battle rebels near Lebanon's northern border with Syria, Hassan Nasrallah said in an address broadcast by Hezbollah satellite TV station al-Manar.
Earlier in the day, 14 people were killed and 230 wounded after a van packed with explosives blew up in a congested commercial and residential area of the Syrian capital near the ancient quarter, Syrian state media said.
"You won't be able to capture Damascus or topple the regime militarily -- the battle is long," Nasrallah said, addressing opponents of Syrian President Bashar Assad.
"Syria has true friends in the region and the world that will not let Syria fall in the hands of America, Israel or Takfiri groups," Nasrallah said in the address.
A Takfiri is a Muslim who accuses another Muslim of apostasy, or deserting the religion.
"How will this happen? Details will come later," he said. "I say this based on information ... rather than wishful thinking."
Nasrallah also warned of uncontrollable, "dangerous retribution" if Syria's Sayyidah Zaynab Mosque is damaged by sectarian violence.
The mosque near Damascus is a shrine Shiite Islam says contains the grave of Zaynab, granddaughter of Muhammad, the chief prophet and central figure of Islam. Sunni Muslims believe her burial place may be a Cairo mosque of the same name.
"If the shrine is destroyed, things will get out of control," Nasrallah said.
His warning Tuesday came six days after fighting between Syrian insurgents and regime forces in the northwestern city of Aleppo left one of the Middle East's most storied mosques severely damaged.
The Great Mosque of Aleppo, the largest and one of the oldest mosques in the city, had a nearly 1,000-year-old minaret destroyed.
Syrian state media said the militant al-Nusra Front Syrian rebel group, also known as Jabhat al-Nusra, had placed explosives inside the minaret, built in 1090.
Rebel activist groups said it was hit by outside artillery fire in an attempt by Assad forces to rout them and retake the mosque.
The anti-Assad groups posted videos on YouTube showing the minaret's rubble strewn over the mosque's tiled courtyard.
The mosque, dating from the beginning of the 8th century, is a UNESCO World Heritage site and widely considered an archaeological treasure but has been part of the larger battleground for months.