147 passengers and 13 employees were on board the train, which belongs to the US state train company Amtrak.
Eight carriages are said to have derailed near Joplin in Montana, according to Amtrak.
Exactly how many were injured is still unclear, but according to the local fire service, at least 15 have needed hospital care, reports NBC.
All those on board have been evacuated, a police source told Reuters.
The accident happened on the railroad that goes by the name The Empire Builder, which operates the Chicago-Seattle route.
The US State Accident Investigation Board will investigate the incident.