The bus came under attack when it was heading to Anba Samuel monastery in the Minya Governorate, 250km south of Cairo.
Twenty four Christians were killed and 27 others injured in the attack, Khaled Megahed, spokesperson of the Ministry of Health, said.
Security forces were searching for the attackers.
No one has claimed responsibility for the attack.
The ambulances rushed to the place of the incident to transfer injured to hospitals.
Two suicide bombings targeting churches in Tanta and Alexandria on April 9 left at least 46 people dead.
Egypt had imposed a nationwide three-month state of emergency after the bombings, with the option to extend for another three months.
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