"The Palestinian people, and all the other nations in the region, chief among them the Lebanese, who have suffered from the Israeli occupation and massacres - they are the ones that bear the burden of the American project of domination [of the Middle East]," the Hezbollah chief said. "The US is responsible for the crimes being committed in Palestine."
The Hezbollah leader said the US "inherited the old colonialist behavior whose goal is to control the Middle East politically, socially, militarily, and culturally."
Nasrallah accused the Americans of wishing to "bring every Muslim under its control so that eventually the nations of the region will recognize Israel."
Though Hezbollah remains an implacable enemy of Israel, it has more pressing matters to deal with in Syria, where its chief ally, President Bashar Assad, has been engaged in a war to stamp out an insurgency by Sunni and Islamist rebels.
Earlier this month, Hezbollah lost a senior commander in Syria, the highest-profile battle death for the group since Lebanon's powerful Shi'ite armed movement joined the war next door, fighting on the side of Assad.
This year, the movement has used the emotionally-charged Ashura, which commemorates the death in battle of the Prophet Mohammed's grandson Hussein, to rally support for its involvement in Syria, where intensified fighting has seen it and Shi'ite backer Iran pay in blood.
Hezbollah fighters are playing a central role in an offensive launched by the Syrian army and its militia allies, taking advantage of air support from Russia which began strikes on the government's foes three weeks ago.
With no end in sight to the conflict that has killed a quarter of a million people, maintaining morale is as important as ever.
Projected live onto a big screen in the hangar in Hezbollah's Beirut stronghold Dahiyeh, Nasrallah thundered against Saudi Arabia, one of the Sunni Muslim states that back the insurgency against Assad.
He described the anti-Assad insurgents as part of a "terrorist project" and Hezbollah's fighters as "men of the resistance" who must fight harder than ever at a critical stage in the battle.
In speeches delivered in the runup to the day of mourning, other clerics stressed the need to stay on the offensive in Syria, rather than let the fight come to Lebanon.
"We've paid in sacrifices much less than it would have cost had they entered our streets and homes. Hezbollah uses its weapons to protect Lebanon abroad," Sheikh Naim Qassem said last week.
Some of Hezbollah's Lebanese opponents say its role in Syria has had the opposite effect, fueling Sunni militancy in Lebanon, which is still recovering from its own 1975-1990 sectarian civil war. But among its supporters, the message rings true.
"These battles are necessary. When Hezbollah goes to fight in Syria.. it's so that Daesh does not come to us in Lebanon. It's a kind of defense," said 43-year-old Mohammed Taher, using an Arabic acronym for Islamic State, the Sunni militant group that controls swathes of Syria and Iraq.
"This fight deserves the martyrdom of any person. I hope we will also be among the martyrs," Taher said, crouching at the back of the hangar.
Hezbollah has already paid for its stepped up involvement in Syria, notably with the death of Hassan al-Haj, killed fighting in Hama province earlier in October.
The veteran commander, described as Hezbollah's most important military figure to be killed in the Syrian war, received a glowing tribute from Nasrallah.
The group's backers Iran have also lost senior military figures in recent offensives, including a veteran general advising Syrian forces fighting Islamic State in Aleppo province.
Ashura marks the death of the Prophet Mohammad's grandson Hussein in a lost battle 1,300 years ago, an event central to the split between Sunni and Shi'ite Islam and marked by Shi'ites around the world with weeping and prayer.
Hezbollah deploys heavy security for Ashura events, setting up roadblocks and checkpoints. Security guards closely shadow any visitors.
The day's message of sectarian mobilization has become more potent since Islamic State emerged as one of the most powerful Sunni groups opposing Assad. Islamic State proclaims Shi'ites heretics who must repent or die.
"It's becoming each year more and more an occasion to send messages, to mobilize," International Crisis Group expert Sahar Atrache said of Hezbollah's observance of Ashura. "Now the rationale is... it's either Assad or the Islamic State. For them it's really an existential war."
About 2,000 people packed the hall, including families with children. Women were separated from men. Enormous posters depicted the battle at Kerbala, in present-day Iraq, where Hussein and his family were killed. People cried tears of devastation as a cleric recited the story of Hussein's death with a trembling voice.
Abu Ali, 60, wearing a black suit, said today's battle in Syria was akin to Kerbala, and must continue: "We are in the right position, we are in the right spot, we are doing the right thing and God willing we will be victorious."
Reuters contributed to this report.