At least three people have died in Biloxi, Miss
Witnesses said it appeared the bus, carrying 50 elderly passengers, was stuck on the track when it was hit.
Biloxi city spokesman Vincent Creel said the bus had left Texas and was passing through the town when it was hit.
The bus was pushed some 300 feet down the road after being struck by the train.
Mr Creel said: "It's very chaotic up here".
Officials said there were several injuries and fatalities but could not immediately clarify.
At least three people have died in the incident
An emergency unit has been set up at a nearby hospital and a helicopter is helping to transport victims.
The local police chief said it was a “terrible, chaotic scene, but it is under the control”.
A majority of the 50 passengers have been injured
He added: "A majority of the 50 have some injuries.”
It is the second time in two months a train has struck a vehicle in the town after a delivery truck was hit after it became stuck on a steep hill.
- Man dies after car struck by train at level crossing in Bedfordshire
- Man dies after car hit by train on level crossing in Gloucestershire
- One dead and at least 20 injured after train derailment in Belgium