Hugh McCulloch was born in Kennebunk, Maine, in 1808. After attending Bowdoin College he studied law in Boston. In 1833 he moved to Fort Wayne, and two years later became the branch manager of the Bank of the State of Indiana. After twenty years as a manager at Fort Wayne he was appointed president of the parent bank in Indianapolis.

McCulloch was for many years a member of the Whig Party. An opponent of slavery, McCulloch joined the Republican Party in 1854. However, McCulloch held racist views and openly told people that he believed whites "were the superior race in intelligence and energy" and deserved to be the "dominant race".

In 1863 Salmon Chase, Secretary of the Treasury, appointed McCulloch as Comptroller of the Currency. When William Fessenden resigned as Secretary of the Treasury in March, 1865, Abraham Lincoln invited McCulloch to take his place. After Lincoln's assassination McCulloch loyally supported President Andrew Johnson. McCulloch claimed at the time that his relations with Johnson were "cordial and intimate, rather more so I think than they would have been with Mr. Lincoln."

McCulloch left office when Ulysses S. Grant became president in March, 1869. Soon afterwards he became a partner in a London banking house. Hugh McCulloch died in Maryland in 1895.