Siskiyou County was formed from parts of Shasta and Klamath Counties in 1852. Klamath County itself ceased to exist in 1875. Parts of Siskiyou County's territory was given to Modoc County in 1855.
According to the U.S. Census Bureau, the county has a total area of 16,440 km² (6,347 mi²). 16,283 km² (6,287 mi²) of it is land and 157 km² (61 mi²) of it is water. The total area is 0.96% water.
As of the census2 of 2000, there are 44,301 people, 18,556 households, and 12,228 families residing in the county. The population density is 3/km² (7/mi²). There are 21,947 housing units at an average density of 1/km² (4/mi²). The racial makeup of the county is 87.07% White, 1.31% Black or African American, 3.90% Native American, 1.19% Asian, 0.13% Pacific Islander, 2.76% from other races, and 3.65% from two or more races. 7.57% of the population are Hispanic or Latino of any race.
There are 18,556 households out of which 27.60% have children under the age of 18 living with them, 51.70% are married couples living together, 10.10% have a female householder with no husband present, and 34.10% are non-families. 28.60% of all households are made up of individuals and 12.80% have someone living alone who is 65 years of age or older. The average household size is 2.35 and the average family size is 2.87.
In the county the population is spread out with 24.00% under the age of 18, 6.70% from 18 to 24, 22.70% from 25 to 44, 28.40% from 45 to 64, and 18.10% who are 65 years of age or older. The median age is 43 years. For every 100 females there are 96.50 males. For every 100 females age 18 and over, there are 94.10 males.
The median income for a household in the county is $29,530, and the median income for a family is $36,890. Males have a median income of $31,936 versus $22,650 for females. The per capita income for the county is $17,570. 18.60% of the population and 14.00% of families are below the poverty line. Out of the total people living in poverty, 26.60% are under the age of 18 and 7.30% are 65 or older.