Spillville was largely settled by Bohemian, German and Swiss immigrants and boasts a strong cultural and musical history.

The Czech composer Antonín Dvorák spent the summer of 1893 in Spillville, where he had Dvorák relatives. There he composed two of his most famous chamber works, including the String Quartet in F (“The American”). Spillville is also the site of the Inwood Ballroom, established in 1920 and the destination of several popular 20th century musicians such as Louis Armstrong, Glenn Miller, Guy Lombardo, and The Byrds. Many tourists to Spillville have also visited the Bily Clocks Museum, a collection of intricately designed clocks created by two brothers in Spillville.

The Roman Catholic parish in Spillville, St. Wenceslaus Church, was built in 1860 and is the oldest Czech Catholic church in the United States. Originally named Spielville after the founder, Joseph Spielmann, it was misread and became Spillville.