Siler, a self-described "Kentucky hillbilly", was born in Williamsburg, Kentucky. Siler was a staunch Republican and hailed from a traditionally Republican region of Kentucky. Siler served in the United States Navy during World War I and in the United States Army as a captain during World War II. His war-time experiences left him, according to David T. Beito, "cold to most proposals to send American troops into harm's way."
Siler attended Columbia University and returned to Williamsburg to be a small-town lawyer. Siler was a devout Baptist and became a renowned preacher. He abstained from alcohol, tobacco, and profanity; and, as a lawyer, rejected clients seeking divorces or who were accused of alcohol-related crimes.
In 1945, Siler was elected a judge of the Court of Appeals of Kentucky. He refused his 150-dollar expense allotment, instead donating it to a special fund Siler set up for scholarships. As a judge, Siler frequently quoted scriptures from the bench. He did the same in his speeches during his 1951 run for governor. This, according to Beito, earned him "a statewide reputation as a 'Bible Crusader.'" Siler was the Republican nominee for Governor of Kentucky in 1951. He was defeated by Democrat Lawrence Wetherby, who won 346,345 votes (54.6%) to Siler's 288,014 (45.4%).
During his tenure in the House of Representatives, which began in 1955, Siler consistently stressed social conservatism. He sponsored a bill to ban liquor and beer advertising in all interstate media. He stated that permitting these ads was akin to allowing the "harsh hussy" to advertise in "the open door of her place of business for the allurement of our school children". Additionally, he was "100 percent for Bible reading and the Lord's Prayer in our public schools".
Like his friend and fellow Republican, Representative Harold Royce Gross, Siler considered himself a fiscal watchdog. He opposed junkets, government debt, and high spending. Siler made exceptions for his home district, however, by supporting flood control and other federal measures that aided his district.
Like Gross, Siler was a Taft Republican (or Old Right Republican) who was opposed to entangling military alliances and foreign interventions. Siler was a consistent opponent of foreign aid; he was one of only two congressmen to vote against John F. Kennedy's call up of reserves during the Berlin crisis. He supported Barry Goldwater in 1964 but did not share his interventionist foreign policy views. This non-interventionism did not seem to bother his constituents.
Siler was critical of U.S. involvement in Vietnam. In 1964, after deciding not to seek reelection, he quipped, in jest, that he would run for President as an antiwar candidate—he pledged to resign after one day in office after ordering the troops brought home. He considered the Gulf of Tonkin Resolution, which authorized President Johnson to take "all necessary steps" in Vietnam, as a "buck-passing" pretext to "seal the lips of Congress against future criticism."
In 1968, the worsening situation in Vietnam prompted Siler to return to politics, unsuccessfully seeking the Republican U.S. Senate nomination. Siler ran on a platform calling for withdrawal of all U.S. troops by Christmas. Ernest Gruening (D.-Alaska) and Wayne Morse (D.-Oreg.), the only two U.S. Senators who voted against the Gulf of Tonkin Resolution, were also defeated that year.In 1985, Cumberland College, in Siler's hometown of Williamsburg, built a men's residence hall named Eugene Siler Hall.