The Biloxi police chief said at least three people died in the incident, with dozens more injured, Blake Kaplan, editor of the Biloxi Sun Herald, wrote on Twitter.
The passengers on the bus were senior citizens traveling from Austin, Texas, to the casino in Biloxi, WLOX-TV reports. Officials said the crossing has flashing lights and crossing gates.
Three people have been confirmed dead, according to the Sun Herald.
The train is believed to have pushed the bus around 300 feet down the track after colliding with it.
He says a nearby hospital is setting up a triage unit at the site to treat the injured. Due to ongoing construction projects involving railroads in the area, there have been multiple incidents of stalling on tracks in Biloxi, local media outlets reported.
First responders were still working to remove people from the bus more than 30 minutes after the crash, which occurred shortly before 2:15 p.m.
The National Transportation Safety Board said it was aware of the crash and monitoring information.