Columbus Delano was born in 1809 in Shoreham, Vermont. He studied the law, established a law practice, and then served as the prosecuting attorney for Knox County, Ohio. Delano was elected to the United States House of Representatives as a Whig in 1844 and served two years, declining to run for a second term. He launched an unsuccessful bid to become governor of Ohio in 1847 and then relocated to New York City, where he ultimately became a partner in a banking firm.

Delano returned to Ohio in 1855, resumed the practice of law, and became a member of the new Republican party. He served as a delegate to the Republican National Convention in 1860, supported Abraham Lincoln's nomination as President of the United States, and, during the Civil War, served as commissary general of Ohio. In 1862, he made a failed bid for election to the United States Senate but was successful, in 1863, in securing a seat in the Ohio state house of representatives. One year later, he returned to the U.S. House of Representatives, where he served from 1865 to 1869 before becoming President Ulysses S. Grant's commissioner of internal revenue.

Delano remained as revenue commissioner until 1870, when he was appointed by Grant to become secretary of the interior. He held that position until 1875, resigning amidst scandal. Columbus Delano then returned to Ohio and served as president of the National Wool Growers' Association and as a trustee of Kenyon College before dying in 1896.