"We have been told that 43 people have been killed," police spokeswoman Charity Charamba told AFP.
"The bus was travelling to Zambia when the driver lost control at a curve yesterday evening," she said.
Charamba said the crash occurred in the Nyamakate area near the border with Zambia.
Cross-border coaches usually ferry traders from Zimbabwe who travel to Zambia to stock up on wares to sell back home.
Last year at least 30 people were killed when two buses collided along the highway connecting the capital Harare and Bulawayo.