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3 year oldCovid and security fears have made this his riskiest visit yet, but the 84-year-old insisted he was "duty bound".
He will try to reassure the dwindling Christian community and foster inter-religious dialogue - meeting Iraq's most revered Shia Muslim cleric.
The Pope will also celebrate Mass at a stadium in Irbil in the north.
About 10,000 Iraqi Security Forces personnel are being deployed to protect the Pope, while round-the-clock curfews are also being imposed to limit the spread of Covid.
On the plane to Iraq, Pope Francis said he was happy to be travelling again, adding: "This is an emblematic trip and it is a duty towards a land that has been martyred for so many years."
He had earlier said Iraqi Christians could not be "let down for a second time", after Pope John Paul II cancelled plans for a trip in 1999 when talks with then-President Saddam Hussein's government broke down.
In the two decades since then, one of the world's oldest Christian communities has seen its numbers plummet from 1.4 million to about 250,000, less than 1% of the population.
Many have fled abroad to escape the violence that has plagued the country since the US-led invasion in 2003 that ousted Saddam.
Tens of thousands were also displaced when Islamic State (IS) militants overran northern Iraq in 2014, destroying their historic churches, seizing their property, and giving them the choice to pay a tax, convert, leave or face death.
The head of the Roman Catholic Church aims to embolden persecuted Christians and call for peace in meetings with political and other religious leaders, reports the BBC's Mark Lowen, who is travelling with him.
Addressing the Iraqi people in a video message on the eve of his trip, Pope Francis said he was "coming as a pilgrim, as a penitent pilgrim, to implore from the Lord forgiveness and reconciliation after years of war and terrorism".
He continued: "I am coming among you also as a pilgrim of peace... seeking fraternity and prompted by the desire to pray together and to walk together, also with our brothers and sisters of other religious traditions, in the steps of Father Abraham, who joins in one family Muslims, Jews and Christians."
Christians, who had some protection under Saddam, later suffered increased attacks by militant Islamists.
In 2010, an attack by jihadists on a Syriac Catholic church in Baghdad left 52 Christians and police dead. Pope Francis will visit the church, Our Lady of Salvation, on Friday.
But the post-Saddam violence has affected all of Iraq's faiths and communities, much of it the result of sectarian tension between majority Shia and minority Sunni Muslims.
Iraq's PM Mustafa al-Kadhimi greeted Pope Francis at the airport, with a red carpet, Iraqis in national dress and songs from a largely unmasked choir.
Hundreds of people lined the airport road as the Pope's convoy, heavily chaperoned by police motorcycles, left for the city.
Security will be massive, with the Pope mostly flying to make his visits, and possibly using an armoured car for shorter trips. In central Baghdad, billboards welcome the Pope, and Iraqi and Vatican flags fly together.
The Christians of Iraq are hoping the Pope will help them overcome discrimination.
Alla Hana Shaba, who fled to Irbil in Iraq's Kurdistan region after the IS invaded the Nineveh Plain in 2014, told Iraqi TV: "We want the Pope to help the displaced find a place to settle. We have lost our houses and money."
Another Christian from the north, Saad al-Rassam, told AFP: "We're hoping the Pope will explain to the government that it needs to help its people. We have suffered so much, we need the support."
Due to security concerns and a sharp rise in Covid-19 infections, the Pope will have limited exposure to the public, our correspondent says.
The Pope himself has had two shots of the BioNTech/Pfizer vaccine, and his entourage will have been inoculated, but there are fears the trip could become a super-spreader event given the large crowds expected.
On Saturday, the Pope will fly south to the Shia holy city of Najaf, where he will visit Grand Ayatollah Ali al-Sistani. The 90-year-old is the prime marja, or spiritual reference, for millions of Shia in Iraq and elsewhere.
Pope Francis will then attend an interreligious meeting at the ancient site of Ur, traditionally believed to be the birthplace of the Prophet Abraham.
Sunday will see him travel to the northern city of Mosul. He will say a prayer of suffrage in Church Square for the victims of the war with IS, which left tens of thousands of civilians dead.
The Pope will also visit nearby Qaraqosh, where Christians have returned since the defeat of IS in 2017 to restore the town's church and rebuild their homes.
That afternoon, he will celebrate Mass at a stadium in Irbil, which thousands of people may attend.
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