The heavily armed Shi'ite Hezbollah movement has been a vital military ally of Syrian President Bashar Assad in the seven-year war.
"We rule out the situation developing into a direct American-Russian clash or a wide state of war," Sheikh Naim Qassem told Lebanese daily al-Joumhouria in an interview.
"The conditions do not point to a total war happening ... unless (U.S. President Donald) Trump and (Israeli Prime Minister Benjamin) Netanyahu completely lose their minds," he said.
Trump has threatened strikes on Syria after a suspected gas attack on a rebel-held town which a Syrian medical relief group said killed at least 60 people, and a Russian envoy voiced fears of a wider conflict between Washington and Moscow.
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Fears of confrontation between Russia, the Syrian state's key ally, and the West ran high after Trump said missiles "will be coming" and lambasted Moscow for standing by Assad.
Trump has tempered those remarks since and even as he consulted allies Britain and France, there were signs of efforts to prevent the crisis from spiraling out of control. The White House said "no final decision has been made" on Syria after Trump met his national security team on Thursday.