It happened just after 5 p.m. in Brookfield, Wisconsin.
The driver of that car, a man in his 60s, was killed, but no one on the train was hurt.
Brookfield police said the car had driven around the train crossing gates.
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The train crossing was expected to be closed for several days due to damage.
Anyone with information on the incident is asked to call Capt. Chris Garcia at the Brookfield Police Department at 262-787-3702.
This is the second time this week that an Amtrak train from Chicago has hit a car on the way to its destination.
Just Wednesday, a train heading to Los Angeles struck a car in Texas.
The driver of the car in that incident also died.