According to the Associated Press, 21 of the train’s 80 cars left the tracks at about 12.02am in Ellicott City, just 13 miles from Baltimore.
The identities of two train operators on the train were not released. However, many media reports by afternoon had identified the fatalities as Elizabeth Conway Nass and Rose Louese Mayr, both 19.
At least a quarter of the cars were estimated to be filled with coal.
Cleanup efforts began Tuesday morning and officials told the news service crews would be searching for other potential victims.
Neither of the women were employees of the railroad. Both were college students at local universities.
Local newspaper, the Greenfield Reporter, said the two posted photos from the train bridge to their Twitter accounts just moments before the incident.
The National Transportation Safety Board has taken over the investigation and is working to determine the cause.
CSX, the second largest US railroad, told AP that the area was closed but that rail traffic in the region was not significantly affected because of available alternative routes.
The coal rail shipper has 21,000 miles of rail in 23 eastern US states and the Canadian provinces of Ontario and Quebec.