The Mounties said emergency crews airlifted one person from the scene with serious injuries after a bus, which was carrying 20 passengers plus the driver, lost control and tipped onto its side into a ditch shortly before 2:30 p.m. on Sunday.
Another nine people suffered what are described as moderate injuries.
The single-vehicle crash occurred about three kilometres south of Neil's Harbour.
Police said they have not yet confirmed what caused the bus driver to lose control.
"Often times, when you have highway closures traffic will simply be rerouted to a secondary road around the collision," said Sgt. Brigdit Leger. "But of course it's the Cabot Trail so there is no secondary highway. So traffic is being turned around."
The Halifax Chronicle Herald reported the bus had Pennsylvania license plates, but the nationalities of the passengers was not immediately known.
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