One of Polk's last acts as President was to sign the bill creating the Department of the Interior. This was the first new cabinet position created since the early days of the Republic. Polk had misgivings about the federal government usurping power over public lands from the states. Nevertheless, the delivery of the legislation on his last full day in office gave him no time to find constitutional grounds for a veto, or to draft a sufficient veto message, so he signed the bill.

Polk was the first president not to keep a pet during his term in office.

In total Polk appointed 10 Article III federal judges, including 2 Justices to the Supreme Court of the United States, 1 judge to the United States Circuit Court of the District of Columbia, and 7 judges to the United States district courts.

Polk was 49 years old when he took the oath of office on March 4, 1845.

True to his campaign pledge to serve only one term, Polk left office in 1849 and returned to Tennessee where he died three months after leaving the White House.

As a child, Polk suffered from urinary stones, and Dr. Ephraim McDowell of Danville, Kentucky, operated to remove them. No anesthetic was available except brandy. The operation was successful, but it might have left James impotent or sterile, as he had no children.