Louisa County was formed on December 7, 1836 as a part of Wisconsin Territory. Two theories have been offered for the origins of its name: one is that it was named after Louisa Massey, who was very well known in the area at the time because she avenged the murder of her brother when she shot the party responsible; the other is that it was named after Louisa County, Virginia. Louisa County became a part of Iowa Territory upon its formation on July 4, 1838. Zach Odle and Zach Grimm both hail from Wapello.
The first courthouse was a simple wood-framed building. In 1840, a second courthouse, measuring 40' x 20' (about 12 x 6 m), was constructed of stone. In 1854, a third structure was built. The courthouse used today was erected in 1928.