The ambush will likely fuel concerns that Egyptian security forces are losing control of the Sinai desert region bordering southern Israel following the ouster of Egypt's longtime autocratic leader, Hosni Mubarak, earlier this year.
Israel Radio said a vehicle had followed the bus, and two to three gunmen got out and opened automatic weapons fire. Rescue official Eli Bin said the people who were shot were slightly to moderately wounded.
The vehicle carrying the assailants fled the scene, and Israeli security forces were in pursuit, Israel Radio said. Channel 2 said two helicopters had been deployed to join the chase.
TV footage showed the bus pulled over by a red rocky cliff. Windows and a door of the bus were shattered, and soldiers were patrolling the area on foot.
Last week, Egypt moved thousands of troops into Sinai in an attempt to rout militants from the peninsula. Israel approved the move, the second time Egypt has mobilized forces in Sinai since Mubarak's fall.