The bus was ambushed by unknown gunmen near a Christian monastery on Friday morning and the Egyptian health ministry said there were dozens of casualties.
A Coptic activist said the bus and an accompanying car were attacked as they drove along an unpaved road towards the St Samuel monastery, around 140 miles south of Cairo, Telegraph reported.
The shooting is the latest in a string of bloody attacks against Egypt’s Coptic minority in the last year, many of them carried out by the Egyptian branch of the Daesh (also known as ISIL or ISIS).
Around 45 people were killed in a pair of suicide bombings at Christian churches on Palm Sunday in April. ISIL claimed credit for the attacks.
An ISIL suicide bomber also killed 29 people in a church in Cairo in December and jihadists have carried out a coordinated campaign of killings against Christians in the Sinai, causing many to flee from their homes.
There are around 10 million Christians in Egypt, making up around 10 per cent of the country's population of 90 million.