The explosion took place at St George's church in the town of Tanta as Coptic Christians were marking Palm Sunday.
Palm Sunday is one of the holiest days in the Christian calendar, and marks the re-entry of Jesus Christ into Jerusalem.
The blast has caused widespread carnage in the Nile delta city of Tanta, north of the capital Cairo.
Christians make up around 10 per cent of Egypt's population and have repeatedly been targeted by Islamic extremists.
ISIS has claimed responsibility for the blast, and also a second attack that took place at a church in the Egyptian city of Alexandria just hours later.
The suicide bombing killed at least 17 people and left 48 injured.
Provincial governor Ahmad Deif told the state-run Nile channel: "Either a bomb was planted or someone blew himself up."
A probe has been launched for any other explosives that could have been planted in the area.
Egypt state media says a bomb has gone off in a church in the Nile Delta, causing casualties
CBC showed footage from inside the church, where a large number of people gathered around what appeared to be lifeless, bloody bodies covered with papers.
Dramatic footage shows the group, of mostly men, shout and run around the church in panic.
Meanwhile, there appears to be blood spatter on the floor.
The explosion took place in the town of Tanta as Coptic Christians were marking Palm Sunday
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The two attacks on Palm Sunday comes after a bombing at Cairo's largest Coptic cathedral in December killed 25 people and wounded 49 – many of them women and children.
At the time it marked the deadliest attack on Egypt's Christian minority in years.
Tanta was also the site of another attack earlier this month when a policeman was killed and 15 were injured after a bomb exploded near a police training centre.
A crowd gathers around in the aftermath of the church bombing in Egypt
Egypt has suffered a series of attacks by militants since 2013 when the military overthrew President Mohammed Morsi.
The leader, from the Muslim Brotherhood, had stirred controversy when he launched a crackdown against Islamists.
And, after he was ousted, some of Mr Morsi's supporters blamed Christians for the coup.
A man stands over one of the victims who died in the blast in Egypt
French President Francois Hollande has expressed solidarity with Egypt following the deadly bombing at the church.
Hollande said "one more time, Egypt is hit by terrorists who want to destroy its unity and its diversity."
He said France "mobilizes all its forces in association with the Egyptian authorities in the fight against terrorism," and offers condolences to the families of the victims.
Meanwhile, Pope Francis also decried the deadly attack on the Coptic church, just weeks before his planned visit to Cairo.
The pontiff expressed his "deep condolences to my brother, Pope Tawadros II, the Coptic church and all of the dear Egyptian nation," and said he was praying for the dead and wounded in the attack.
Word of the bombing came as Francis himself was marking Palm Sunday in St. Peter's Square.
The pontiff asked God "to convert the hearts of those who spread terror, violence and death, and also the hearts of those who make, and traffic in, weapons."
People gather near the Coptic Church, which is the main Christian Church in Egypt
The Coptic Orthodox Church is the main Christian Church in Egypt.
Most Copts live in Egypt, but the Church has about a million members outside of the country.
A shift in Islamic State's tactics from attacking soldiers and police to targeting Christian civilians has become a potential turning point in a country trying to halt a provincial insurgency from spiralling into wider sectarian bloodshed.
A large number of people gathered outside the scene as an ambulance attended to the wounded
Egypt's Christian community has felt increasingly insecure since Islamic State spread through Iraq and Syria in 2014, ruthlessly targeting religious minorities. In 2015, 21 Egyptian Christians working in Libya were killed by Islamic State.
Copts face regular attacks by Muslim neighbours, who burn their homes and churches in poor rural areas, usually in anger over an inter-faith romance or the construction of a church.
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