Although Ingersoll claimed to hate politics, and he never gained public office, his powerful speaking style made him an effective campaigner for other politicians.  In 1860, he was an unsuccessful Democratic candidate for Congress before his abolitionist and Unionist views compelled a switch to the Republican Party during the Civil War.  Ingersoll failed to secure Republican nominations for Congress in 1864 and 1866 and for the Illinois governorship in 1868.

At the onset of the Civil War, Ingersoll raised and commanded the 11th Regiment of the Illinois Volunteer Cavalry.  He saw action at the Battle of Shiloh (April 6-7, 1862), but was later captured on December 18.  When a prisoner exchange was not forthcoming, he resigned from the Union Army on June 30, 1863, and was allowed to return to Illinois.  In 1864, Ingersoll campaigned for Republican candidates, including his brother, Ebon, who was elected to Congress.

After the war, Ingersoll backed the Reconstruction policies of the Radical Republicans, and during the 1866 elections, he gained national fame as a leading stump speaker.  While still an aspirant for public office, he hid his religious skepticism in rhetoric extolling liberty and progress as the objects of his devotion:  "Human Liberty is the shrine at which I worship.  Progress is the religion in which I believe."  But by 1872, in a speech called "The Gods," Ingersoll was arguing that all forms of divinity were human constructions, and he was soon taking pride in labeling himself a "heretic" and "infidel."

During the 1870s and 1880s, Ingersoll was one of the most prominent lawyers in the United States, defending federal government officials implicated in the Whiskey Ring and Star Route scandals.  At the 1876 Republican National Convention, he delivered a rousing speech nominating Senator James Blaine for president.  The silver-tongued orator dubbed Blaine “a plumed knight" for defending both the Union cause as a Civil War congressman and, more recently, the senator’s own reputation against scandalmongers.  After Blaine lost, Ingersoll campaigned enthusiastically for the Republican nominee, Governor Rutherford B. Hayes of Ohio.  In 1877, religious groups prevented President Hayes from naming Ingersoll as U.S. minister to Germany.

Although Ingersoll expressed the possibility of human immortality in a eulogy for his brother in 1879, he continued to speak and publish as the nation's foremost agnostic.  In an age when the American political and public cultures were permeated by religious talk, he attracted attention as a sort of village atheist writ large, collecting large fees as a popular public lecturer.  Besides "Hell" (1878; in which he denied its existence), Ingersoll's orations include, "Some Mistakes of Moses" (1880), "The Great Infidels" (1881), "Myth and Miracle" (1885), and "Why I Am an Agnostic" (1896).  He died in New York City in 1899, and his family insisted he did not renounce his religious skepticism.