The accident took place late last night near the city of Edfu, north of the Aswan governorate, a local health ministry official said.
The bus was en route to Cairo and five children were among the 19 dead in the accident, the official.
The provincial governor has cancelled Aswan's National Day festivities, which falls on the week starting January 15, to mourn the dead, the state-run MENA news agency reported.
The celebrations mark the inauguration anniversary of the Aswan High Dam, one of the biggest projects in Egypt's modern history.
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Five people died last week in a road accident in the southern governorate of Qena.
Around 12,000 people die annually on Egypt's roads, according to a 2012 World Health Organisation (WHO) report.
Egypt is one of ten countries listed in the WHO Road Safety project to be conducted over five years by a consortium of six international partners.