John Slidell was born in New York City in 1793.
Slidell was a brother of Alexander Slidell Mackenzie, a naval officer who commanded the USS Somers on which a unique event occurred in 1842 off the coast of Africa during the Blockade of Africa. Three crewmen were hanged after being convicted of mutiny at sea. Mackenzie reversed the order of his middle and last names to honor a maternal uncle.
Another brother, Thomas Slidell, was chief justice of the Louisiana Supreme Court. He was also the brother-in-law of the American naval Commodore Matthew C. Perry, who was married to Slidell's sister, Jane. Perry is remembered for opening United States trade with Japan in 1853.