The attack comes as Egypt's vital tourism industry is showing signs of recovery after years in the doldrums because of the political turmoil and violence that followed a 2011 uprising that toppled former leader Hosni Mubarak.
Prime Minister Mostafa Madbouli visited the injured tourists in hospital, where he announced that the tour guide had died from his wounds.
An interior ministry statement said 10 other tourists from Vietnam and the Egyptian bus driver were wounded when the homemade device exploded at 6:15 pm (1645 GMT).
Photos on social media showed the right side of the bus caved in and peppered with shrapnel.
"The police forces have left to go to the scene, the circumstances are being clarified", the ministry said.
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Over the past two years, militant attacks against Christians in Egypt - usually targeting churches or buses carrying pilgrims to remote desert monasteries - have killed over a hundred people.
Egypt has for years been battling an insurgency in North Sinai, which surged following the 2013 military ouster of president Mohamed Morsi.
The last deadly attack on foreign tourists in Egypt was in July 2017, when two Germans were stabbed to death in the Red Sea resort of Hurghada.
Those events and the bombing of a Russian airliner shortly after it took off from Sharm el-Sheikh in 2015 caused tourist numbers to plunge.