Edmund graduated from Yale in 1757 and studied law in New York, before moving by 1761 to North Carolina, where his brother Dr. William Fanning was the first rector of St. George's Parish in Northampton County. In 1762, Edmund was admitted to the bar after studying two years under the attorney general. He settled in Hillsborough to practice law and represented Orange County in the assemblies of 1762, 1766, 1767, and 1768; and the borough of Hillsborough in 1770 and 1771. He served as the register of deeds, 1763-1768, and was also a judge of superior court and a militia colonel. Besides donating a bell to the local Anglican church, he led efforts to find Hillsborough a minister, schoolmaster, town clock, and marketplace. In an effort to improve educational opportunities for local youth, he became the first president of Queen's College, the earliest American university south of Virginia. Because of its affiliation with the Presbyterian Church, the British monarchy refused to grant it a charter and the college ultimately failed, but not before schooling a young orphaned lad with few prospects: future U.S. president Andrew Jackson, who later destroyed an invading British army at the Battle of New Orleans. While it is clear that Edmund was a great favorite of North Carolina's colonial governor William Tryon, there is no evidence to support the claim found in many texts that Tryon was Edmund's father-in-law. Tryon only had one daughter, Margaret, who was just ten years old in 1771, the last year Tryon was governor of North Carolina. While back in England in 1791, she tried to elope with a military officer, but while climbing down a rope ladder, slipped and fell to her death.

Despite his obvious energy and talents, Edmund was soon resented by some of the local inhabitants due to his enthusiastic efforts to collect taxes. At the time, backcountry North Carolina was populated mainly by Germans, Scotch-Irish, or Welsh who had moved to the area to lead simple lives free of government interference. Soon an underground movement was formed to combat the rising influence of Anglo culture, with Edmund becoming a primary symbol of their wrath. After Edmund dealt them a series of defeats in the courtroom and at the ballot box, these people, known as Regulators, resorted to a campaign of violence to keep their grip on power. A series of riots, arsons, and public beatings followed, which quickly escalated into a widespread insurrection. In September 1770, a group of Regulators seized Edmund and horsewhipped him. Onlookers were certain that he would be murdered by the mob, but he suddenly broke free by "manly exertion" and barricaded himself in a store. His frustrated adversaries then looted and burned down his house (see historic marker). Alarmed by this and other atrocities, the North Carolina assembly passed an act which declared the Regulators guilty of treason and made them liable to execution. Armed with this new legislation, Governor Tyron assembled a militia of approximately one thousand men to put down the Regulator movement, with Edmund being given command of one of the columns. Despite being outnumbered 2-to-1, the governor skillfully crushed his disorganized and poorly armed opponents at the Battle of Alamance on May 16, 1771. During the two hour skirmish, nine men on each side were killed and scores were wounded, plus seven prisoners were executed later. This battle effectively ended the movement, but the resulting publicity inspired many leaders in New England and is seen as a key event leading up to the American Revolution. Today the former battlefield, located six miles south of Burlington, is recognized as a North Carolina Historic Site (see picture) and is open to visitors, who can view the multimedia orientation program and battlefield monuments (see picture).

The unfortunate loss of life added to Edmund's unpopularity in some quarters, but almost immediately afterwards Tyron left to become governor of New York and Edmund followed him, accepting a position as his personal secretary, and eventually rising to the lucrative position of surveyor general. Having sustained substantial losses from the destruction of his property in North Carolina, Edmund applied for reparations from the legislature there through Tryon's successor, Governor Martin, but bad feelings remained and the petition was unanimously rejected, with Martin being rebuked for "trifling with the dignity of the house" for presenting it. Perhaps seeing the stormclouds of the American Revolution on the horizon, Edmund decided to apply for the office of Chief Justice of Jamaica, but the position went to someone else. At the beginning of the American Revolution, he was living in New York City, but revolutionaries drove him from his home and he was forced to seek refuge aboard the HMS Asia in the harbor. In December of 1776, at the request of the British commander-in-chief Sir William Howe, Edmund raised a celebrated regiment of Loyalists called the King's American Regiment, in which his nephew John Wickham, the prominent Richmond attorney, served. Their heaviest fighting was in the Carolinas, where they were involved in the capture of Charleston, and the battles of Camden and King's Mountain. The regiment was disbanded in Saint John, New Brunswick in the fall of 1783, with several hundred officers and soldiers settling there as Loyalists. During the course of the war, Edmund was wounded twice and suffered the seizure of his property. He tried to avoid the latter by giving some of his holdings to close friends, with the understanding that they would sell the property after the war and forward the funds to him, but predictably the result was a legal morass that dragged on for years. In July, 1779, as British troops under Governor Tryon were preparing to burn Yale University, Edmund successfully intervened to save his beloved alma mater from destruction, and was later thanked by the school with an honorary degree.

Ironically, another one of Edmund's nephews, Nathaniel Fanning, became an important hero for the Patriot cause. He was a son of Edmund's brother Gilbert, a Long Island native who became a prominent Connecticut merchant and Patriot who matched Edmund in the fervor for his cause and who was one of the largest provisioners of Washington's army. Nathaniel was born on May 31, 1755 in Stonington, Connecticut and served as a midshipman and second-in-command under John Paul Jones, father of the American Navy, aboard the USS Bonhomme Richard in its brilliant victory over the HMS Serapis, which occurred just off the coast of Flamborough Head, England on the evening of September 23, 1779 under a harvest moon (see picture). This epic victory has arguably become the most celebrated of all American naval engagements, immortalized by Jones' retort "I have not yet begun to fight!" when his surrender was demanded part-way through the three-and-a-half hour battle after the British captain, Richard Pearson, mistakenly believed the Americans were on the brink of defeat. At the start of the bitter battle in which nearly half of both crews were killed, it seemed the Americans were hopelessly outgunned by the much more heavily armed enemy frigate, but they neutralized the British advantage by brazenly pulling alongside and lashing the two ships together. With the British cannons firing at pointblank range, the fighting became so intense that several of the American crew became panic-stricken and tried to surrender the ship, but were met by a furious Jones who shouted "Shoot them! Kill them!," but finding his pistols previously discharged, had to settle for bludgeoning them into submission. The fighting hinged on the success of close-quarter combat for control of the entangled yards high above the decks, an operation commanded by Nathaniel. Most of the men in his original party were killed, but he led a fresh group aloft, cleared the enemy tops of their men, and then boldly crossed over onto the yards of the other ship, where his men used their new perch to strafe the deck below with grenades and mortars, causing a great slaughter and driving the British from their stations. Finally one of the grenades bounced down an open hatchway containing munitions, causing an enormous explosion and compelling the ship to surrender.

The USS Bonhomme Richard was so riddled by cannon fire that it soon sank despite the best efforts of its men, and the crew was forced to transfer over to the HMS Serapis. Although several well funded expeditions have been mounted to find it, the ship's remains have never been positively located, and the USS Bonhomme Richard remains the world's most sought after shipwreck. After the battle, Jones recommended that Nathaniel be promoted, declaring that he was "prominent in obtaining the victory." Nathaniel, who participated in numerous other campaigns, wrote a book about his exploits and the U.S. Navy has named a number of ships in his honor (see USS Fanning FF-1076). He died of yellow fever on September 30, 1805 while serving as a lieutenant in command of the USS Gunboat No. 1. Although fortune smiled on Nathaniel during the American Revolution, two of his brothers, Gilbert and Thomas, were captured aboard a privateer and confined to the HMS Jersey, a notorious prison ship where scores died from mistreatment. Gilbert was killed during a prison escape attempt, while Thomas became dangerously ill, until Edmund, hearing of the news, arranged for his release and medical care, allowing him to return home to his parents fully recovered. Another of Nathaniel's brothers, Edmund, was a famous trader and explorer who circumnavigated the globe in 1798 and discovered several uncharted islands in the Pacific, including Fanning Island and Washington Island. He commanded or acted as directive agent for over seventy expeditions to the South Seas and China, before his death in New York City on April 23, 1841, at age 71. His Voyages around the World, first published in 1833, became a popular seller.

In 1783, Edmund became lieutenant-governor of Nova Scotia, and on November 30, 1785 he married Phebe Maria Burns of Digby Neck and they eventually had three daughters and a son, although his son died unmarried at only age 23 shortly after returning from military service in the East Indies, causing Edmund immense grief. In 1786, Edmund became governor of Prince Edward Island, a position he held for nearly nineteen years, until 1805, the longest term of any governor for the province. His assumption of this latter position was marked by an unusual conflict where the previous governor, Walter Patterson, was caught up in a land scandal and refused to surrender the reigns of power, despite being dismissed by the British government. For several months the stalemate dragged on, until fresh instructions from England confirmed Edmund's appointment. During his tenure as governor, he was especially active in championing higher education, personally donating land for what later became the University of Prince Edward Island. Edmund's house in the capital of Charlottetown was one of the grandest in the area, until it was destroyed by fire in 1855. He was made a major general in the British army in 1793, lieutenant general in 1799 and general in 1808. The honorary degree of A.M. was given him by Harvard in 1764 and by Kings (now Columbia) in 1772; the degree of D.C.L. by Oxford in 1774; and the honorary degree of LL.D. by both Yale and Dartmouth in 1803. After announcing he would retire to London, a testimonial provided by some of the area's leading citizens was published in the February 16, 1805 edition of The Royal Herald which noted "in the pure and genuine language of our hearts, that we cannot sufficiently express our deep regret at your retirement" and expressed hope "that you will still make us happy by returning and residing amongst us."