Pepin County was created by a special act of the Wisconsin Legislature on February 25, 1858; ten years after Wisconsin became a state. Before that, Pepin was part of Dunn County, and before that, part of Chippewa County. The lands including Pepin County were acquired by the Federal government by treaty with the Dakota Indians in 1837.

The Eastern Dakota were the principal inhabitants of this region when the first European explorers began to arrive here. These explorers kept journals and diaries and wrote letters about their adventures. With their arrival, Pepin County's written history began.

Pierre Esprit Radisson, an early French explorer, is believed to have been writing about the Eastern Dakota in his journal in the mid-1600's, referring to them as the “Nation of the Beef”. He described them as living in a town with large cabins covered with skins and mats. They subsisted by hunting bison, large herds of which are believed to have roamed the Chippewa River Valley, and which may explain why Radisson called them the Nation of the Beef. They also harvested wild rice and exploited other abundant flora and fauna of the riverine environment.

Another Frenchman, Nicolas Perrot, described the Eastern Dakota as living in swampy territory, “…nothing but lakes and marshes full of wild oats…in a tract 50 leagues square with the Mississippi River flowing through the middle.” Perrot could have been talking about the Chippewa River delta at the foot of Lake Pepin.