Tillman was born near Trenton, South Carolina. He left school in 1864 to join the Army of the Confederate States of America during the American Civil War but was disabled by an illness; he never served in the Confederate Army and lost an eye during treatment. During Reconstruction he became a paramilitary fighter in the struggle to overthrow the interracial Republican coalition in the state and disempower the black majority; he was present at the Hamburg Massacre in July, 1876, during which black Republican activists were murdered by Tillman's fellow "Red-shirts."

Posing as the friend of ordinary white farmers, Tillman began a "Farmers Movement" in the 1880s. He was elected Governor of South Carolina in 1890 and served from December 1890 to December 1894. He helped establish Clemson College and Winthrop College while in office.

He was largely responsible for calling the State constitutional convention in 1895, which disfranchised most of South Carolina's black men through the use of so-called Jim Crow laws. As Tillman proudly proclaimed in 1900, "We have done our level best ...we have scratched our heads to find out how we could eliminate the last one of them. We stuffed ballot boxes. We shot them. We are not ashamed of it." (Logan, p. 91)

He was elected as a United States Democratic Party member to the United States Senate in 1894, and was reelected in 1901, 1907, and 1913, thus serving from the day he took office, 4 March 1895, until his death. A hotheaded and intemperate debater, Tillman was known as "Pitchfork Ben" during his years in the Senate. Although frequently described by historians and later observers as "populist" or "a populist," Tillman was in fact a steadfast opponent of the Populists (the People's Party) of his day, fearing that their national program for agricultural renewal would empower black Southerners. During that time period, he was censured by the Senate in 1902 after assaulting another Senator on the Senate floor, became the chairman of the Committee on Revolutionary Claims (57th through 59th Congresses), served on the Committee on Five Civilized Tribes of Indians (61st and 62nd Congresses), and the Committee on Naval Affairs (63rd through 65th Congresses). During World War I, impatient with the Navy's requests for larger battleships every year, he ordered the United States Navy to design "maximum battleships," the largest battleships that they could use.

Tillman opposed American annexation of the Philippines because he feared an influx of non-white immigrants would result, undermining white racial purity.

Tillman died in Washington, DC and is buried in Ebenezer Cemetery, Trenton, South Carolina.

He was one of the most outspoken and unapologetic advocates of racism ever to serve in Congress.