According to the U.S. Census Bureau, the county has a total area of 1,864 km² (720 mi²). 1,855 km² (716 mi²) of it is land and 9 km² (3 mi²) of it (0.48%) is water.
Knox County was named in honor of Henry Knox, the first Secretary of War.
The first "Knox County" in Illinois is unrelated to the modern incarnation. In 1790, the land that was to become Illinois was divided into two counties: St. Clair and Knox. The latter included land in what was to become Indiana. When Knox County, Indiana was formed from this portion of the county in 1809, the Illinois portions were subdivided into counties that were given other names.
The modern Knox County, Illinois, was organized in 1825, from Fulton County, itself a portion of the original St. Clair County.
As of the census of 2000, there were 55,836 people, 22,056 households, and 14,424 families residing in the county. The population density was 30/km² (78/mi²). There were 23,717 housing units at an average density of 13/km² (33/mi²). The racial makeup of the county was 89.86% White, 6.29% Black or African American, 0.19% Native American, 0.69% Asian, 0.01% Pacific Islander, 1.57% from other races, and 1.39% from two or more races. 3.40% of the population were Hispanic or Latino of any race.
There were 22,056 households out of which 27.70% had children under the age of 18 living with them, 51.40% were married couples living together, 10.60% had a female householder with no husband present, and 34.60% were non-families. 29.60% of all households were made up of individuals and 14.10% had someone living alone who was 65 years of age or older. The average household size was 2.33 and the average family size was 2.87.
In the county the population was spread out with 22.00% under the age of 18, 9.80% from 18 to 24, 26.50% from 25 to 44, 24.10% from 45 to 64, and 17.50% who were 65 years of age or older. The median age was 39 years. For every 100 females there were 99.20 males. For every 100 females age 18 and over, there were 96.60 males.
The median income for a household in the county was $35,407, and the median income for a family was $44,010. Males had a median income of $32,151 versus $21,662 for females. The per capita income for the county was $17,985. About 7.70% of families and 11.10% of the population were below the poverty line, including 16.80% of those under age 18 and 6.00% of those age 65 or over.