A major factor in the growth of Pickens County is its location along major transportation corridors. Access to Interstate 85 on its way to Charlotte and Atlanta is easy and plentiful. US 123 speeds traffic into Greenville, or toward Atlanta, and four-lane U. S. 76 cuts travel time to Anderson. Scenic Highway 11 forms a loop from I-85 in Gaffney through the Upcountry, bisecting I-26 in Spartanburg County, passing through scenic northern Pickens County and returning to I-85 at the Georgia line. US Highway 178 passes north and south through the middle of Pickens County, providing easy access to the mountains of Western North Carolina.
Norfolk and Southern Railroad is the major rail carrier, with a busy mainline through Clemson, Central, Liberty and Easley, and CSX Transportation also is available in the area.

At least 10 trucking companies operate out of Pickens County. More than 75 others serve local business and industry from neighboring counties.

The Greenville-Spartanburg International Jetport, located on 3,360 acres between Greenville and Spartanburg, is less than an hour's drive from most of Pickens County. It is served by twelve airlines offering service to and from more than 20 major cities with 63 daily departures and 17 nonstop destinations. GSP also offers two federal inspection stations for international travelers.

The Pickens County Airport, north of Liberty on US 178, provides easy access for private planes with a 5,000-foot runway and an expansion program that has seen more than $7 million in improvements to the runway and taxiway system in the past decade.

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