Grand Ayatollah Mohammed Hussein Fadlallah told Iraqis that their vote was "an Islamic responsibility" that would ward off the internal and external dangers threatening their country.
In a statement released on Thursday, Fadlallah, the top religious authority for Lebanon's 1.2 million Shias, said his fatwa was in response to questions put to him by Iraqis asking whether they should vote on the constitution.
"I call upon you - in my religious capacity - to fully participate in the popular referendum on the basis of a political responsibility in choosing the constitution that fulfills all the aspirations and interests of the Iraqis and which is based on Iraq's unity," the fatwa said.
Fadlallah, 69, an Iraqi-born Lebanese who lived for more than 30 years in the Iraqi holy city of Najaf, has followers in Iraq and communicates with Shia clerics in the country. He enjoys wide respect among Shia Muslims - though his popularity in Iraq is unclear.
The fatwa came as Iraqis on Thursday began picking up copies of the draft constitution that they will vote on 15 October, after the country's Shia-led parliament ended a bitter dispute with Sunni legislators about how the referendum will be conducted.
Sunni Arab leaders were mobilising to defeat the charter at the polls.
Sunni Arab leaders of Iraq are
seeking to defeat the charter
Addressing Iraqis, Fadlallah said in his fatwa: "The Islamic responsibility you bear before God is the preservation of Iraq's unity and its Muslim and Arab identity, which is open to the Iraqis who belong to other religions, and its independence and freedom, which reject any occupation.
"This is in addition to taking into account the reasons for Islamic unity to confront a sectarian strife for which the enemies of a free and united Iraq are planning," he said.
Iraq's Shia majority and the Kurdish minority overwhelmingly support the constitution.
Sunni Arabs make up only 20% of the population but can still defeat the constitution if they get a two-thirds "no" vote in any three of Iraq's 18 provinces. There are four provinces where they have a chance of doing so.
Fadlallah is a harsh critic of US policies in the region, where many Arabs consider America biased towards Israel in its conflict with the Palestinians.