John Nelson was born in Frederick, Maryland, on June 1, 1791, and attended the College of William and Mary, where he graduated in 1811.

From 1820 until 1822 Nelson was a U.S. Congressman. His only other public office prior to becoming President John Tyler's third attorney general (July 1, 1843-March 3, 1845) was that of U.S. charge d' affairs to the Kingdom of the Two Sicilies.

Following his departure from Washington at the end of the Tyler administration, he seems to have disappeared, and little is known about his activities before he died on January 8, 1860.