The first settler to the area was Benjamin Crowley of Kentucky who arrived in 1821 and established a home about 12 miles west of Paragould.
Greene County was formed on 5 November 1833 out of portions of Lawrence County, Arkansas and contained portions of present Clay County, Arkansas and Craighead County, Arkansas. The county was named after Revolutionary War hero Nathanael Greene. The original county seat was in Benjamin Crowley's home. By 1836 when Arkansas became a State the county seat was located at a settlement called "Paris".
In 1848 a national highway was put through and the county seat was moved to the community of Gainesville, Arkansas which had a reputation as a relatively lawless town. The county seat remained there until 1883 when it was moved to the new town of Paragould. The residents of Gainesville opposed the move and it is reported that shots were fired and tempers were high. A new courthouse was built in 1888 and the building still survives in downtown Paragould.
According to the U.S. Census Bureau, the county has a total area of 1,501 km² (580 mi²). 1,496 km² (578 mi²) of it is land and 6 km² (2 mi²) of it is water. The total area is 0.37% water.
As of the census2 of 2000, there are 37,331 people, 14,750 households, and 10,708 families residing in the county. The population density is 25/km² (65/mi²). There are 16,161 housing units at an average density of 11/km² (28/mi²). The racial makeup of the county is 97.45% White, 0.13% Black or African American, 0.42% Native American, 0.17% Asian, 0.02% Pacific Islander, 0.47% from other races, and 1.34% from two or more races. 1.16% of the population are Hispanic or Latino of any race.
There are 14,750 households out of which 33.10% have children under the age of 18 living with them, 59.20% are married couples living together, 9.70% have a female householder with no husband present, and 27.40% are non-families. 24.00% of all households are made up of individuals and 11.00% have someone living alone who is 65 years of age or older. The average household size is 2.49 and the average family size is 2.95.
In the county the population is spread out with 25.20% under the age of 18, 9.10% from 18 to 24, 28.70% from 25 to 44, 23.10% from 45 to 64, and 13.90% who are 65 years of age or older. The median age is 36 years. For every 100 females there are 95.30 males. For every 100 females age 18 and over, there are 91.90 males.
The median income for a household in the county is $30,828, and the median income for a family is $37,316. Males have a median income of $27,535 versus $20,375 for females. The per capita income for the county is $16,403. 13.30% of the population and 9.90% of families are below the poverty line. Out of the total people living in poverty, 15.40% are under the age of 18 and 12.80% are 65 or older.