He was born on his father's plantation on the Savannah River in Horse Creek Valley in Edgefield County, South Carolina.

Pickens championed the construction of roads and canals by government, a policy called internal improvements.

After leaving office, Pickens moved to Alabama and helped negotiate a treaty with the Creek Indians of Georgia.

Pickens died June 24, 1838, in Pontotoc, Mississippi, and was interred at Old Stone Church Cemetery in Clemson, South Carolina.

[3] His son, Francis Wilkinson Pickens (1805–1869) was a U.S. Representative and the Governor of South Carolina when the state seceded from the Union in 1860.