At the beginning of the Civil War, fewer than 10 percent of Pulaski County's population consisted of black slaves. Many county residents were Southern sympathizers, but the majority of the population supported the Union. Two important Civil War battles, Mill Springs and Dutton's Hill, took place within the county's boundaries. Neither was especially destructive to life or property. Somerset was occupied by a Union garrison for a portion of the war and was raided by Confederate Gen. John Hunt Morgan and his cavalry. Toward the end of the war, engineers and surveyors from the Union army visited Pulaski to map out a roadbed for a military railroad, and their survey reached as far as Point Isabel on the Cumberland River. Point Isabel was renamed Burnside in honor of the Union general. In 1866 the U.S. War Department established a permanent national cemetery in western Pulaski County near the site of the Civil War engagement of Mill Springs, where over six hundred Union dead were buried. Less than a mile to the south is a Confederate cemetery, near where Confederate Gen. Felix Zollicoffer fell during the Battle of Mill Springs.

In the years after the Civil War, Pulaski County became a political bastion of the Republican party. Thomas Z. Morrow, of Somerset, was one of the founders of Kentucky's Grand Old Party. In its history, only three Democrats-Andrew Jackson, James Buchanan, and Woodrow Wilson-have carried Pulaski County in a presidential contest. From Lincoln's second election in 1864, the Republican majority for president has exceeded 60 percent in almost every election. County residents in the twentieth century have also voted Republican in state and local elections.

In 1877 the Cincinnati & Southern (now Norfolk Southern) Railway came to Pulaski County, which led to rapid growth in Somerset, Ferguson, Burnside, and other towns along the right-of-way, and to virtual abandonment of many of the county's smaller hamlets. Afterward came large logging and sawmill operations. The period of industrial activity peaked when the Cincinnati & Southern ("Queen and Crescent") opened its Ferguson repair yard. For over a generation, the railroad and the shops were an economic mainstay. A sleepy county seat with only 587 people in 1870, Somerset swelled to be a regional metropolis by 1900 with almost 6,000 people.

At the turn of the century, Pulaski County's Edwin Porch Morrow, future governor (1919-23), began his political rise. A familiar figure at numerous Republican national conventions, Morrow was a formidable orator, and after losing by only 471 votes in the 1915 governor's race, Morrow returned to the political wars in 1919 to upset the incumbent governor, James D. Black (1919). After his election, an estimated 10,000 people gathered around the Pulaski County Courthouse to congratulate the only governor the county has produced.

Pulaski County's population reached its peak in 1920 and thereafter began a slow decline which was not reversed until the 1960s. Despite a relatively high county birth rate, young residents of Pulaski and other rural counties emigrated for jobs offered by Cincinnati's Procter & Gamble and Detroit's booming automobile industry.

John Sherman Cooper began his long career of service to the county, state, and nation as the Great Depression worsened. In the 1930s, Cooper served as county judge and watched as Pulaski tax receipts fell from $95,000 in 1930 to $57,000 by 1936. In the depression's bleakest days, 2,000 county families received federal food commodities. In 1933 the Pulaski County sheriff sold 460 farms for nonpayment of taxes. Before the Great Depression ended, Franklin D. Roosevelt's New Deal poured $800,000 in aid into the county.

After World War II, the Southern Railroad closed the Ferguson shops, but the completion of Wolf Creek Dam and the creation of the vast Lake Cumberland opened new possibilities for fishing, recreation, and tourism. By the 1960s the county's economy became more diversified with several small industries producing clothing, charcoal, houseboats, and automobile parts. In the 1980s, Pulaski County evolved into a regional business, medical, and educational center. Most of the county, however, remained rural and as of 1985 contained 2,400 farms which produced large quantities of pork, beef, poultry, milk, corn, soybeans, and tobacco. Many Pulaski Countians who have city jobs live in rural areas. Ever since 1798, most residents have been Baptist and the Flat Lick congregation in eastern Pulaski County is as old as the county itself. In 1990 about ninety of the county's 140 churches were Baptist.

Burnside's Harriette Simpson Arnow dealt in her novels with Kentuckians confronting the early twentieth century. The Dollmaker (1954), her most famous work, examined the human cost of the migration of Kentuckians to the factories of the north. Her novels and historical works, Seedtime on the Cumberland (1960) and Flowering of the Cumberland (1963), gave Pulaski County a place in American literature.