It was named after James Madison (1751–1836), the fourth President of the United States (between 1809 and 1817).

[4] Hiram Hurst was the first European-American settler in Madison County, having come from Missouri about April 15, 1846.

Madison County is home to the only highway tunnel in Iowa, Harmon Tunnel, through the neck of an incised meander of the Middle River in Pammel Park.

[15] The population ranking of the following table is based on the 2020 census of Madison County.

From 1880 to 1960, the county only failed to back the party's candidate in 1932 when Herbert Hoover was defeated in a national landslide for reelection by Franklin D. Roosevelt.

The county was much more of a swing area between 1964 and 1996, voting for the national winner in every presidential election between 1964 and 2004 aside from 1988 when Michael Dukakis was boosted to an inflated margin of victory statewide by a farm crisis.

Since the start of the third millennium, Republicans have carried the county in every presidential election.

Donald Trump also produced the county's strongest Republican presidential victory since 1952 in 2016, winning by a margin of over 30 percent.