Three major towns in Saline County are connected by U.S. Route 45, and formerly by the now-abandoned Cairo and Vincennes/Big Four/New York Central Line, from north to south: Eldorado, Harrisburg, and Carrier Mills.

The Saline River flows through the central point of the county in three forks: North, Middle, and South.

[5] As of the 2010 United States census, there were 24,913 people, 10,379 households, and 6,631 families residing in the county.

There were 11,697 housing units at an average density of 30.8 per square mile (11.9/km2).

[11] In terms of ancestry, 17.8% were Irish, 16.6% were German, 12.9% were American, and 11.1% were English.