For years, Poplar Bluff served as a division point for the railroad, a "home away from home" for train crews whose runs originated in either Little Rock or St. Louis. Numerous railroad hotels and boarding houses lined the streets near the Missouri Pacific station, and the railroad was the major employer in the city. Today, diversified industries and tourism have replaced the railroad payroll in importance, and Poplar Bluff serves as the Amtrak stop for nearby cities in southeast Missouri.

The Amtrak station is located in the former Missouri Pacific depot in downtown Poplar Bluff. This is an unstaffed station; the waiting area is unlocked prior to train time. A public pay telephone is available inside the station.