A bomb hidden beside a wall went off as the bus carrying 14 Vietnamese tourists was passing.
Three of the tourists were killed along with the tour guide, an Egyptian citizen, Attorney General Nabil Ahmed Sadeq said in a statement.
The two dead were Vietnamese holidaymakers would had been visiting the pyramids near the capital Cairo, according to the country's interior ministry, which confirmed 10 more were wounded.
No group took immediate responsibility for the incident.
Prosecutors said they had launched an investigation "to arrest the perpetrators".
Egypt's Ministry of Interior announced on Saturday morning that it has killed 40 terrorists during raids on three terrorist hideouts in Giza and North Sinai.
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At least 154 people are missing, more than 1,400 people were injured and thousands of people have moved to higher ground. In 2018, the country has suffered its worst annual death toll from disasters since 2004's devastating tsunami.
Another 12 people, including 10 tourists, were injured in the attack that occurred in the Mariutiya neighborhood of Giza, the statement said.
"We were going to the sound and light show and then suddenly we heard a bomb".
The bus driver later told local media he had not deviated from the route.
The injured were taken to the nearby Haram hospital, Reuters news agency reports.
Security forces have since February been conducting a major operation focused on the Sinai Peninsula, aimed at wiping out a local IS branch.
Egypt's government says it is prioritising fighting Islamist militants, as it works to restore stability after years of turmoil following the Arab Spring protests of 2011.
Two German tourists were stabbed to death at a hotel in the popular Red Sea resort of Hurghada previous year.