The northbound train struck a Jeep Cherokee at a railroad crossing in Valhalla, about 20 miles north of New York City, Metro-North Railroad spokesman Aaron Donovan said. Killed were the Jeep's driver and five people aboard the train, he said.
The train shoved the Jeep about 10 train car lengths north, and the Jeep and the front of the train caught fire, he said.
The rail passengers were moved to the rear of the train, which had left Grand Central Terminal about 45 minutes earlier.
Passengers got off from the rear of the train. About 400 of them were taken to a local rock climbing gym for shelter. Buses were heading there to pick them up and take them to their destinations.
The railroad track gates came down on top of the vehicle, which was stopped on the tracks, the Metro-North spokesman said. The driver got out to look at the rear of the vehicle, then she got back in and drove forward and was struck, he said.
Smoke was seen pouring out of the scorched rail car, its windows blackened.
Stacey Eisner, a passenger in the rear of the train, told NBC News that she felt the train "jerk" and then a conductor walked through the train explaining what had happened. She said her train car was evacuated about 10 minutes later using ladders to get people out.
Service on Metro-North's Harlem Line has been suspended between Pleasantville and North White Plains.
Metro-North is the nation's second-busiest railroad, after the Long Island Rail Road. It was formed in 1983 and serves about 280,000 riders a day in New York and Connecticut.