For the Kurds, the vote presents an opportunity to finally break away from Iraq.
"We have the right to choose our destiny and fulfill our dream," Dallo Mohammed, a 32-year-old accountant from the town of Khanaqin, told NBC News. "I am a Kurdish citizen, this is how I was born, and this is how I would die."
But opponents of the vote — a list of countries that includes the U.S. — say the ballot could provoke destabilization, ethnic violence, and hamper the fight against ISIS.
They are the world's largest ethnic group who occupy one geographical area but don't have their own country.
They are mostly Sunni Muslims and their estimated population of 35 million spans a huge mountainous region across Iran, Iraq, Syria, Turkey and Armenia.
They were given hope of their own nation after World War I when the 1920 Treaty of Sevres carved up the Ottoman Empire and eked out a proposed state for Kurdistan.
Disagreements and subsequent treaties meant that never happened.
Today, depending on which country they find themselves in, the Kurds are subject to a complex web of adversaries, allegiances and internal divisions.
In Turkey and Iran, they face discrimination and their organizations have been blacklisted as terrorists. In Iraq and Syria, however, they have proved among the most effective fighters pushing back ISIS, and they have received the backing of the Pentagon in both arenas.
While the situation in Syria is far more messy, in Iraq the Kurds have established their own semi-autonomous region. Iraqi Kurdistan is an oil-rich province that encompasses one-third of the country and has emerged as the most secure area in an otherwise chaotic state.
Monday's referendum is asking people whether they want to expand this autonomy and become a fully fledged, independent country.
More than 3 million people are expected to participate, according to The Associated Press
"They see this as a once-in-a-century opportunity to begin the process of forming their own state," said Gareth Stansfield, a senior associate fellow at London's Royal United Services Institute, a London-based think tank.
The Kurds have threatened to break off from the rest of Iraq for years.
They accuse the central government of violating its constitutional obligations toward them and withholding their share of the federal budget.
"From World War I until now, we are not a part of Iraq," Kurdish President Masoud Barzani told the Guardian on Friday. "It’s a theocratic, sectarian state. We have our geography, land and culture. We have our own language. We refuse to be subordinates."
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Right now may be their best shot at independence thanks to a confluence of events — namely the weakening of political systems surrounding them following two decades of violence and the rise of ISIS in 2014.
But even in the event of a "yes" vote, the government says it won't separate right away. Rather, it sees the vote more as a statement of intent, a springboard from which to launch dialogue with the central Iraqi government.
The vote will cover not only areas in the official, semi-autonomous region but also disputed regions where the Kurdish forces, known as the peshmerga, have pushed into following their largely successful campaign against ISIS.
These peshmerga — whose name means "those who face death" — have been fighting alongside the Iraqi army in the U.S.-led coalition, but it is the Kurds who have proved the far more effective fighting force.
The central government in Baghdad has rejected the referendum as illegal and unconstitutional. Its Supreme Court has officially suspended the ballot — not that the Kurds are listening — and Prime Minister Haider al-Abadi has threatened military action if the vote leads to violence.
In a televised address from Baghdad on Sunday night, al-Abadi said that "the referendum is unconstitutional. It threatens Iraq, peaceful coexistence among Iraqis and is a danger to the region."
Some Arab Iraqis, such as 44-year-old electrician Ali Hameed, believe the vote will bring more uncertainty to what is already a perilously fractious region.
"This will create more problems for them," said Hameed, who spoke to NBC News in his home city of Baghdad. "Iran and Turkey will sooner or later have a reason to invade northern Iraq, and we know the Kurds do not have capabilities to fight" a war against those countries.
The prospect of violence doesn't deter Mohammed Ali, a 36-year-old Kurdish pharmacist from Irbil, the capital of Iraqi Kurdistan. He told NBC News his people would be prepared to stand up for their beliefs in the event of a military flare-up.
"The only thing I am afraid of is that if the government in Baghdad tried to stand in our way," he said. "This might be the cause of a civil war between the Kurds and Arabs. The Kurds will fight for this, they will fight for their rights."
Nechirvan Barzani, the Iraqi Kurdish prime minister and nephew of the president, has dismissed the possibility of violence. He told Kurdish network Rudaw: "I do not see any military attack at all on the Kurdistan Region. It is impossible to happen."
There has been enormous outside pressure on the Iraqi Kurds to postpone the vote or cancel it entirely.
Turkey and Iran issued a joint statement with Iraq saying they were considering deploying "countermeasures," although they didn't say what these might be.
Both countries are worried that an independence vote might inspire an upsurge in separatism among their own Kurdish populations.
Turkey has for years been locked in conflict with the Marxist militant separatist Kurdistan Workers Party, commonly known as the PKK, and it has also been fighting the Kurds in Syria, who it sees as an extension of its own rebels.
To get an idea of how truly complex this picture is, the U.S. is a NATO ally of Turkey, but the Pentagon is also arming the Syrian Kurds, even though Turkey and the Kurds have been fighting each other.
In Iraq, Turkey's relationship with the Kurdistan Regional Government is more nuanced. Whereas Turkey opposes its own Kurds, it has forged strong military and economic ties with those in Iraq. Crucially these ties involve a pipeline that runs from landlocked Kurdistan to the Turkish port of Ceyhan.
"After [the referendum], let's see through which channels the northern Iraqi regional government will send its oil, or where it will sell it," President Recep Tayyip Erdogan said in Istanbul on Monday according to Reuters. "We have the tap. The moment we close the tap, then it's done."
Turkey is also conducting military exercises along its border with Iraqi Kurdistan, and Erdogan confirmed this was no coincidence.
"Our military is not [at the border] for nothing," he added Monday, according to an AP report. "We could arrive suddenly one night."
That Turkey hasn't intervened already has led some to suggest that while it doesn't want to openly support the referendum, in private it might see it as a positive step in its pragmatic and transactional relationship.
"Turkey could have easily stopped [the referendum] in its tracks simply by threatening to close the oil pipeline for extended periods of routine maintenance," Stansfield wrote in a paper for RUSI earlier this month.
"This has not happened," he said. "This raises the possibility that the Kurdish view may be right — that Turkey is publicly positioning itself to be unsupportive ... but privately sees several benefits in embracing independence."
Although the Department of Defense has found the Iraqi and Syrian Kurds to be a ruthless anti-ISIS force, this has not translated to White House support for independence.
"The United States strongly opposes the Iraqi Kurdistan Regional Government’s referendum on independence," State Department spokeswoman Heather Nauert said Wednesday.
The U.S. sees the possibility of a fracturing Iraq as a destabilizing force in an already unsettled region politically — not to mention hampering the ongoing fight against ISIS.
"The costs of proceeding with the referendum are high for all Iraqis, including Kurds," Nauert added. "Already the referendum has negatively affected ... coordination to dislodge ISIS from its remaining areas of control in Iraq."
Many Kurds don't see it that way. They see a country that, referendum or not, is already flawed and has not worked in their interests for decades.
"The region is already not stable," said Omar Khoshnau, a 38-year-old salesman from Irbil, the capital of Iraqi Kurdistan. "The war against ISIS is going to be more effective if Kurdistan is an independent state, because it is an ally for the international community, and we are the first who fought ISIS."
A nod for independence would be no doubt symbolic but its practical implications are harder to pin down.
The referendum question asks: "Do you want the Kurdistan region and the Kurdistani areas outside the region’s administration to become an independent state?"
But it has no formal framework or mechanism for how this might work. Instead, the president has said the decision will be the trigger for meaningful dialogue with Baghdad.
According to Marianna Charountaki, a lecturer in Kurdish politics at Britain's University of Leicester, the vote is mainly figurative anyway.
"The reality is that there's already de facto independence and now we're just talking about the outward appearance and official titles," she said.
There are many sticking points including disputed areas that the peshmerga pushed into after the Iraqi army abandoned fled as ISIS rampaged across the country. These include the key, oil-rich city of Kirkuk.
Alexander Smith is a senior reporter for NBC News Digital based in London.