Caldwell County has been witness to several major events in its history. In the early nineteenth-century Caldwell County witnessed the forced migration of the Cherokee on the Trail of Tears. The Cherokee spent several weeks in Caldwell County during the winter of 1838, notably at Big Springs in downtown Princeton, Skin Frame Creek, and the Centerville area near Fredonia. In 1860, the construction of Princeton College began but was soon delayed by the Civil War. Confederate troops camped on the grounds of Princeton College and used one of the buildings as a hospital. Later, in 1864 Confederates burned the courthouse in Princeton. The establishment of railroads in the late nineteenth century allowed Princeton to become an important junction on several major railway lines.
Around the turn of the century, an agricultural boon in dark leaf tobacco had made Caldwell, especially along with Christian County, a major tobacco growing center. However, the monopolization of the tobacco market by James B. Duke left many farmers financially strapped and discontented. Under the organization of Dr. David Amoss of Cobb in Caldwell County, a vigilante group formed called the Night Riders. The Night Riders terrorized those who cooperated with the tobacco conglomerate by destroying crops, burning warehouses, and physical intimidation. The "Black Patch Wars" came to an end around 1908.
By the middle of the twentieth century Caldwell County began the shift from agriculture to industrialization. Though Caldwell County is still largely agricultural today it is home to several major factories including Bremner, the largest private label cookie and cracker factory in North America.
Since 1925, Caldwell County has been home to the University of Kentucky's College of Agriculture. With extensive experiment farms, the College of Agriculture in Princeton is a leader in horticultural and biological sciences in the twenty-first century.