Local emergency crews fought to control the fire which broke out at 01:00 p.m. local time. According to local media reports, at least 16 train cars were derailed.
Several homes, including the Dupo High School, in the local area were evacuated as a precautionary measure and residents were housed at a nearby shelter, according to US-based media reports.
St. Clair County Emergency Management Agency confirmed its team was dealing with the incident, but did not specify what caused the explosion.
Posted on Facebook: "First responders are on scene of a multiple train car derailment on Carondelet Ave in Dupo. We will post updates as they become available." Dupo is a small town on the Mississippi River some 10km south of downtown St Louis.
There have been no reports of injuries during the incident.