The crash occurred at the crossing of a state highway and the Iowa Interstate Railroad in a rural area about 70 miles (113 kilometers) east of Des Moines, according to Poweshiek County Sheriff Matt Maschmann.
One person in the semi-truck died and another was transported with "serious injuries," Maschmann said in a statement.
Seventeen train cars and two power engines derailed after the crash and caused "significant damage" to the railroad, he said. Images of the scene showed a massive heap of railcars with billowing smoke.
No hazardous material was spilled, according to Iowa State Patrol spokesman Sgt. Alex Dinkla.