The state-owned Andhra Pradesh State Road Transport Corp bus was trapped in Vutukuru village.
Some passengers climbed on top of the bus as the water level rose, desperately looking for help. The administration could not launch rescue operations due to massive flooding.
District Collector Kantilal Dande was making efforts to arrange a helicopter for rescue operation, official sources said.
Several areas were inundated in Guntur and other districts in Andhra Pradesh due to heavy rains lashing the region since Wednesday.