The Territorial Legislature created Jackson County on Jan. 12, 1852, from the southwest part of Lane County and the unorganized area south of Douglas and Umpqua Counties. The county was named after President Andrew Jackson.

Jackson County's borders originally ran south to California, west to the Pacific Ocean, east to Lane County, and north to Umpqua and Douglas Counties. The boundaries of the county were changed reflecting the creation of Coos, Curry​, Josephine, Klamath, Lake and Wasco Counties. Currently, Jackson County includes 2,801 square miles and its boundaries extend to California in the south, Josephine County in the west, Douglas County in the north, and Klamath County in the east.

Modoc, Shasta, Rogue River and Umpqua Indian tribes lived in the present boundaries of Jackson County. In the early 1850s, both the Klickitats from the north and the Deschutes from the south raided and settled the area. Gold discoveries in the Rogue and Illinois River valleys in the 1850s and completion of a wagon road connecting the county with California to the south and Douglas County to the north led to an influx of non-native settlers. Conflict between the Americans and Indians led to war in 1856 resulting in hundreds of casualties and the removal of the Rogue River tribe to the Siletz Reservation. During the next two years, several small bands of Indians were transferred to the Grande Ronde Reservation west of Salem.

Jacksonville was designated as the first county seat in 1853. However, the city declined due to diminishing returns in the local goldfields and the construction in the 1880s of the Oregon and California Railroad, which bypassed the city. Medford, located five miles east of Jacksonville, benefited from the location of the railroad and the accompanying commerce and development. Jacksonville fended off suggestions to move the county seat until 1927 when Medford was finally selected as the county seat. 

The first county courthouse was a white two story frame structure built in 1854 in Jacksonville. In 1883 a two-story red brick building was built and served as the courthouse until the county government moved to Medford in 1927. A new courthouse was dedicated in 1932 and continues to house county offices in Medford. In 1978 the current three-story justice building was constructed to house the court system.

The first county officials were appointed in March, 1853. These officers included three county commissioners, a county clerk, a sheriff, a prosecuting attorney and a treasurer. An assessor and surveyor were added later. 

The voters of Jackson County approved a home rule charter at the general election, Nov. 7, 1978. The primary organizational change was a governing body consisting of a board of three commissioners, which continues to constitute the legislative and principal policy making agency of the county. A county administrator is responsible for overall county management, policy implementation, financial planning, and staff to the board of commissioners. The elected officials include the county commissioners, sheriff, justice of the peace, district attorney, assessor, clerk and surveyor. The treasurer's duties were assumed by the finance department as a result of a 1999 charter amendment.

Jackson County's 2013 population of 206,310 represented a 1.5% increase over 2010. 

The county's principal industries are agriculture, manufacturing and recreation. Major points of interest include the Shakespearean Festival, Historic Jacksonville, Southern Oregon University, the Peter Britt Music Festival, the Rogue River, Lithia Park and the Crater Lake Highway.