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The vehicle smashed through a barrier and plummeted around six metres (20 feet) onto a dry river bed south of the central city of Indore in Madhya Pradesh state.
"At least 21 people have died," a senior police official said, without wishing to be named.
The dead included three children and 10 women, the Times of India newspaper reported.
The bus driver had fallen asleep at the wheel before the crash and had fled the scene, the daily said.
India accounts for 11 percent of the global road death toll despite only having one percent of the world's vehicles, according to a World Bank report released in 2021.
The same report estimated there are about 150,000 car crash fatalities in India annually, or one person every four minutes.
