The crash occurred at 7:41 p.m., on the Bypass in Rocky Point between 25A and Broadway, police said.
A police spokesman said the tour bus was traveling west on the Bypass and the Toyota was traveling east. The Toyota briefly went off the road, then swerved back onto and directly across the road in front of the bus.
The bus hit the Toyota on the passenger side, and "pushed the vehicle for a distance, and they both went into the shoulder of the road," the spokesman said.
The bus driver was taken to John T. Mather Memorial Hospital in Port Jefferson with non-life-threatening injuries.
Neither the bus nor the sedan appeared to be carrying passengers, police said. However, Seventh Squad detectives were still investigating.