Greenville is a gateway to the eastern third of North Carolina and is mainly an agricultural and trading center with a strong tobacco presence. Some employment categories have declined, partially due to cutbacks in the tobacco industry, but the economy is in transition and future job-growth projections are among the highest in the state. A wide assortment of other manufacturing activity, from pharmaceuticals to material handling equipment, is located in the area.

While East Carolina University provides a regional medical center and raises the level of educational attainment, most cultural amenities and services are found in Raleigh to the west. Greenville does have a strong local parks and recreation infrastructure. The area is a gateway to the coastal areas of the Outer Banks and Cape Hatteras, 100-plus miles to the east.

Greenville is located just above sea level on a flat coastal plain along the banks of the Tar River. Surrounding areas are agricultural with deciduous woods and tidewater marshes to the east. The climate is humid subtropical with a slight marine influence. Summer is sunny, hot, and humid, with more 90 degrees-plus days than most towns in North Carolina.

Winters are cool and fairly wet, but the area is close enough to the ocean and sheltered enough by the Appalachians to escape extreme cold; however, temperatures drop below freezing 45 times each winter. Annual rainfall is high, but snow is rare. First freeze is late October, last is mid-April.