According to the company's statement, the Amtrak train traveling from Los Angeles to Chicago with 243 passengers struck a dump truck and derailed.
The crash occurred at an "uncontrolled intersection" on a gravel road without lights or electronic controls.
Cpl. Justin Dunn, a spokesperson for Missouri State Highway Patrol Troop B, told reporters that two of the people who were killed were aboard the train while the third was in a dump truck that the train struck.
Authorities said the tragic incident happened at an uncontrolled intersection without warning lights or motion gates where a gravel road crossed the railroad tracks southwest of the town.
A school has been turned into a triage center for victims with minor injuries, officials said.
Governor Mike Parson said, "We are saddened to hear of the Amtrak train derailment in Chariton County this afternoon. We ask Missourians to join us in praying for all those impacted."