The RCMP in Nova Scotia say 10 people were injured in the crash and three of them suffered serious injuries.
The Cabot Trail, a scenic route used by tourists, was closed Sunday afternoon after the bus carrying 20 passengers rolled onto its side about three kilometres south of Neil's Harbour.
"It was very serious for the people involved but it could have been a lot worse," said Greg Organ, chief of the Neil's Harbour-New Haven Volunteer Fire Department.
Organ said the crash happened on a section of the highway that is accessible to firefighters and four people were airlifted to area hospitals.
"There are many, many places where if the bus went off the road it would be a recovery," he said, describing the numerous steep slopes along the scenic highland highway.
Organ said the bus's licence plate was from Pennsylvania and most of the passengers were senior citizens.
RCMP Cpl. Scott MacRae said the passengers on the bus ranged in age from 40 to 80 years old.
He said the bus is owned by Executive Coach Inc. in Lancaster, Pa., and all the tourists on the bus are believed to be from the United States.
The company declined comment on the accident.
The Mounties restricted public access to the Cabot Trail while police, fire and medical crews responded to the accident.
Police said the bus was removed and the trail was re-opened to traffic early Sunday evening.
Note to readers: This is a corrected story. A previous version said the Jaws of Life were used by firefighters.