The tourists were heading to a sound and light show at the pyramids, which they had visited earlier in the day, said Lan Le, 41, who was also aboard the bus but unhurt.
“We were going to the sound and light show and then suddenly we heard a bomb. It was terrible, people screaming,” she told Reuters, speaking at Al Haram hospital, where the injured were taken. “I don’t remember anything after.”
Egypt’s interior ministry said the bus was hit by an explosion from an improvised device hidden near a wall at around 1815 local time (1615 GMT).
About two hours later the vehicle could be seen behind a police cordon with one of its sides badly damaged and the windows blown out, a Reuters reporter said.
Dozens of police, military and firefighters were at the site, on a narrow sidestreet close to the ring road, where traffic was moving normally.
Shortly afterward, workers brought a pick-up truck to tow the bus away.
An investigator at the scene said the device had likely been planted near the wall.
The interior ministry confirmed the death of two of the tourists, and the state prosecutor’s office later said a third had died. In total, 14 Vietnamese tourists had been traveling on the bus, it said.
Prime Minister Mostafa Madbouly told local TV from Al Haram hospital that the guide had died from his injuries.
“The bus deviated from the route secured by the security forces,” Madbouly told Extra News channel, an assertion also made by the owner of the company that organized the bus tour.
“We have been in contact with the embassy of Vietnam to contain the impact of the incident, and what is important now is to take care of the injured,” the prime minister said.
The bus driver later told local media he had not deviated from the route.
Egypt’s army and police launched a major campaign against militant groups in February, targeting the Sinai Peninsula as well as southern areas and the border with Libya.