Hassan Nasrallah acknowledged for the first time that his powerful Shiite group was fighting across all of Syria in support of President Bashar al-Assad's regime.
And he called specifically on his fiercest critics in Lebanon to back his intervention across the border, warning that their support for Assad's opponents would not save them from jihadists.
"Today we are facing a kind of danger that is unprecedented in history, which targets humanity itself," Nasrallah said, speaking ahead of Monday's anniversary of the withdrawal of Israeli troops from Lebanon in 2000.
"This is a danger to everyone. No one should bury their heads in the sand.
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"We invite everyone in Lebanon and the region to take responsibility and confront this danger and end their silence and hesitation and neutrality."
The speech was a full-throated defence of Hezbollah's role in Syria, where it has acted as a key force multiplier for Assad's embattled regime since an uprising that began in March 2011.
But Nasrallah has always framed Hezbollah's intervention as protecting Lebanon from the threat of extremism.
And today, he said the choice in Syria as between jihadists from IS and Al-Qaeda affiliate Al-Nusra Front, or the regime and its allies like Hezbollah.
Nasrallah dismissed the US-led coalition fighting against IS, saying the jihadists continued to move freely despite its air strikes.
He directed much of his speech to members of Lebanon's Future movement, which is fiercely opposed to Hezbollah and its role in Syria, warning they would be the "first victims of IS and Al-Nusra" if they arrive in Lebanon.