Long was the first physician to use ether to anesthetize a patient in surgery. Long performed his ground-breaking surgery in 1842, but the credit for the first public demonstration of the anesthetic effects of ether went to William Thomas Green Morton, who demonstrated its use in 1846.

Long was born November 1, 1815, in Danielsville, Georgia, to James and Elizabeth Long. He received his bachelor's degree from the University of Georgia in Athens, Georgia, in1835, and his Doctor of Medicine degree from the University of Pennsylvania School of Medicine in 1839. After a year and a half practicing medicine in several hospitals in New York City, he returned to Jefferson, Georgia, a small, country town, where he became a general practitioner. In August, 1842, he married Caroline Swain. They had six children.

Long performed his famous surgery a few months before he was married. For years, people had known that nitrous oxide (laughing gas) and ether made people feel exhilarated and intoxicated. Some people even held "ether frolics," or parties in which they inhaled ether for fun. Long had been to such parties, and had noticed that people suffered no pain if they fell down. One of Long's acquaintances, James M. Venables had used ether himself at social events, and wanted some cysts removed from his neck. In his office on the evening of March 30, 1842, Long soaked a towel with ether and had Venables inhale it. While Venables was unconscious, Long surgically removed his cysts. When Venables woke up, he was surprised that he had no cysts and no pain. Long charged Venables $2 for the surgery and anesthesia. Long continued to use ether in minor surgical procedures and obstetrics for years to come, but he did not publish his discovery until 1849, three years after William Thomas Green Morton had created a huge stir in Boston, Massachusetts, with his public demonstration of the powers of ether.

In 1850, Long moved back to Athens, Georgia. There he spent the rest of his life, practicing medicine. He died in Athens on June 16, 1878.