It is believed that a Ford Focus car crashed into a Stagecoach bus, flipped over and landed on its roof outside the Gorse Hill pub.
A number of other cars were also hit in the collision.
"The male driver of the Focus died at the scene," a GMP spokesperson said.
"The driver of the bus, the driver of a second car and another casualty have been taken to hospital for treatment to serious injuries."
Several bus passengers are being treated for "less serious injuries", GMP said, and emergency services are at the scene.
Police have closed off Chester Road between Talbot Road and Great Stone Road and motorists have been advised to avoid the area.
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