Trempealeau County is in the western part of Wisconsin, on the Mississippi River. It is bounded on the east by Jackson County, on the north by Eau Claire County, on the west by Buffalo County, as well as by Winona County across the Mississippi River in Minnesota. The area belongs entirely to the Mississippi system, and is separated into three distinct divisions, the Trempealeau Prairie Region, the Trempealeau Valley Region and the Beef River Region. The county was created Jan. 24, 1854.

The history of a State, or a county, writes author J. B. Alexander, "is almost entirely the history of the people who constitute the inhabitants." Indeed, Alexander devotes a substantial portion of his History of Mecklenburg County from 1740 to 1900 to biographical sketches of former citizens of the county, often giving such information as date and place of birth, parents' names, date of arrival in Mecklenburg County, education, profession, military service, and names of spouse and children. Many of these Mecklenburg residents descended from the Scotch-Irish immigrants who populated the early settlements of the county, which was formed in 1762 and originally encompassed a large area that included what is now Union, Cabarrus, Gaston, Lincoln, Cleveland, and Rutherford counties, as well as the upper portions of present-day South Carolina. Later waves of immigration brought settlers from Maryland, Pennsylvania, Germany, and Ireland to the area.

Charles Martin's 1881 history of Door County, Wisconsin, provides a brief survey of the early history of the county, as well as descriptions of the towns of Washington, Otumba (Sturgeon Bay), Forestville, Gibralter, Chambers' Island, Brussels, Liberty Grove, Clay Banks, Nasewaupee, Sevastopol, Bailey's Harbor, Gardner, Union, and Jacksonport. Brief biographical sketches of county residents and a county business directory are included.