The crash happened just before 3 a.m. on Highway 59 and Interstate 610.
Police said the driver of the Dodge Ram was traveling west on 610 and took the exit ramp to head north on 59 when they somehow lost control as they turned.
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The car flipped over the edge, landed on the street below, and began to spark, causing a fire.
Officials arrived on the scene and discovered the driver's body.
The victim has yet to be identified.
Police said they do believe the crash involved only one vehicle.