Mediapolis was first a train station for the city of Kossuth, Iowa at a point on the Burlington, Cedar Rapids and Minnesota Railway (later part of the Chicago, Rock Island and Pacific) between Burlington, Iowa and Wapello, Iowa. Media, meaning "middle," was apponded to polis, meaning "village," as Mediapolis is half way between Wapello and Burlington.
From 1875 to the mid 20th century, Mediapolis was a railroad junction where the Burlington and Northwestern Railway to Washington, Iowa (later a branch of the Chicago, Burlington and Quincy) met the original north-south line.
The Rock Island Railroad ceased operation in 1980, leading to the abandonment of the north-south line through Mediapolis. One heavy industry remains 2 miles southwest of town, the United States Gypsum Sperry mine. This is a shaft mine 620 feet deep, opened in 1961 and employing around 200 people in 2010. Of these, only 25 to 50 actually work in the mine. Underground, the mine extends 1.5 miles west and 1.75 miles south of the shaft. This is a room and pillar mine with 37-foot pillars separating roads 37 feet wide on a square grid.
There is also some light manufacturing in town, and it serves as a bedroom community for both Burlington and Muscatine, Iowa.
The highway has cut through the town ever since the highway has been under operation by the federal government.