It was created on March 28, 1835 and fully organized on April 4, 1836. It was named after Genesee County, New York by settlers from New York.  Many local place names in the county are also from New York and Pennsylvania, reflecting the pattern of settlement. A major attraction for visitors is Crossroads Village, a living history village north of Flint.
In July 2010, the County Board voted for the clerk and register of deeds offices to merger on January 1, 2013. On October 26, 2010, Genesee County became a founding member of the Karegnondi Water Authority.
According to the 2000 census, the county has a total area of 649.34 square miles (1,681.8 km2), of which 639.64 square miles (1,656.7 km2) (or 98.51%) is land and 9.70 square miles (25.1 km2) (or 1.49%) is water.
Most of the land in the county is very flat, but the southern end is hilly and covered by several lakes.
The county is mostly drained by the Flint River, which is dammed into Mott Lake and the Holloway Reservoir in the northeast corner of the county. The southeast corner and southern end are drained by the Shiawassee River.
The 2010 United States Census indicates Genesee County had a 2010 population of 425,790. This is a decrease of -10,351 people from the 2000 United States Census. Overall, the county had a -2.4% growth rate during this ten-year period. In 2010 there were 169,202 households and 111,620 families in the county. The population density was 668.5 per square mile (258.1 square kilometers). There were 192,180 housing units at an average density of 301.7 per square mile (116.5 square kilometers). The racial and ethnic makeup of the county was 72.7% White, 20.5% Black or African American, 0.5% Native American, 0.9% Asian, 3.0% Hispanic or Latino, 0.1% from other races, and 2.2% from two or more races.
There were 169,202 households out of which 32.6% had children under the age of 18 living with them, 43.3% were husband and wife families, 17.2% had a female householder with no husband present, 34.0% were non-families, and 28.4% were made up of individuals. The average household size was 2.48 and the average family size was 3.03.
In the county the population was spread out with 25.0% under age of 18, 8.9% from 18 to 24, 24.7% from 25 to 44, 27.6% from 45 to 64, and 13.7% who were 65 years of age or older. The median age was 39 years. For every 100 females there were 93.1 males. For every 100 females age 18 and over, there were 89.4 males.
The 2010 American Community Survey 1-year estimate indicates the median income for a household in the county was $38,819 and the median income for a family was $48,979. Males had a median income of $27,269 versus $18,082 for females. The per capita income for the county was $19,860. About 16.9% of families and 21.0% of the population were below the poverty line, including 31.0% of those under the age 18 and 6.3% of those age 65 or over.
The county government operates the jail, maintains rural roads, operates the major local courts, keeps files of deeds and mortgages, maintains vital records, administers public health regulations and safeguards public health, and participates with the state in the provision of welfare and other social services. The county board of commissioners controls the budget but has only limited authority to make laws or ordinances. In Michigan, most local government functions — police and fire, building and zoning, tax assessment, street maintenance, etc. — are the responsibility of individual cities and townships.
Genesee County except for the City of Flint is covered under the jurisdiction of the 67th District Court of Michigan. District Courts have a limited jurisdiction as charged under state law. 67th District Court operates in seven divisions, each with a single judge except for the Central Court Division, which is used for jury and felony cases.