Edward Gibbon was born in 1737, the son of Edward and Judith Gibbon at Lime Grove, in the town of Putney, Surrey. He had six siblings: five brothers and one sister, all of whom died in infancy. His grandfather, also named Edward, had lost all of his assets in the South Sea Bubble stock market collapse (1720), but eventually regained much of his wealth, so that Gibbon's father was able to inherit a substantial estate. As a youth, his health was under constant threat. He described himself as "a puny child, neglected by my Mother, starved by my nurse." At age nine, Gibbon was sent to Dr. Woddeson's school at Kingston upon Thames, shortly after which his mother died. He then took up residence in the Westminster School boarding house, owned by his adored "Aunt Kitty," Catherine Porten. Soon after she died in 1786, he remembered her as rescuing him from his mother's disdain, and imparting "the first rudiments of knowledge, the first exercise of reason, and a taste for books which is still the pleasure and glory of my life." By 1751, Gibbon's reading was already voracious and certainly pointed toward his future pursuits: Laurence Echard's Roman History (1713), William Howel(l)'s An Institution of General History (1680 – 85), and several of the 65 volumes of the acclaimed Universal History from the Earliest Account of Time (1747 – 1768).

Following a stay at Bath in 1752 to improve his health, at the age of 15 Gibbon was sent by his father to Magdalen College, Oxford, where he was enrolled as a gentleman-commoner. He was ill-suited, however, to the college atmosphere and later rued his 14 months there as the "most idle and unprofitable" of his life. But his penchant for "theological controversy" (his aunt's influence) fully bloomed when he came under the spell of rationalist theologian Conyers Middleton (1683 – 1750) and his Free Inquiry into the Miraculous Powers (1749). In that tract, Middleton denied the validity of such powers; Gibbon promptly objected. The product of that disagreement, with some assistance from the work of Catholic Bishop Jacques-Bénigne Bossuet (1627 – 1704), and that of the Elizabethan Jesuit Robert Parsons (1546 – 1610), yielded the most memorable event of his time at Oxford: his conversion to Roman Catholicism on June 8, 1753. He was further "corrupted" by the 'free thinking' deism of the playwright/poet couple David and Lucy Mallet; and finally Gibbon's father, already "in despair," had had enough.

Within weeks of his conversion, the youngster was removed from Oxford and sent to live under the care and tutelage of Daniel Pavillard, Reformed pastor of Lausanne, Switzerland. It was here that he made one of his life's two great friendships, that of Jacques Georges Deyverdun (the French language translator of Goethe's The Sorrows of Young Werther); the other being John Baker Holroyd (later Lord Sheffield). Just a year and a half later, after his father threatened to disinherit him, on Christmas Day, 1754, he reconverted to Protestantism. "The articles of the Romish creed," he wrote, "disappeared like a dream." He remained in Lausanne for five intellectually productive years, a period that greatly enriched Gibbon's already immense aptitude for scholarship and erudition: he read Latin literature; traveled throughout Switzerland studying its cantons' constitutions; and aggressively mined the works of Hugo Grotius, Samuel von Pufendorf, John Locke, Pierre Bayle, and Blaise Pascal.

He also met the one romance in his life: the pastor of Crassy's daughter, a young woman named Suzanne Curchod, who would later become the wife of Louis XVI's finance minister Jacques Necker, and the mother of Madame de Staël. The two developed a warm affinity; Gibbon proceeded to propose marriage, but ultimately wedlock was out of the question, blocked both by his father's staunch disapproval and Curchod's equally staunch reluctance to leave Switzerland. Gibbon returned to England in August 1758 to face his father. There could be no refusal of the elder's wishes. Gibbon put it this way: "After a painful struggle I yielded to my fate: I sighed as a lover, I obeyed as a son." He proceeded to cut off all contact with Curchod, even as she vowed to wait for him. Their final emotional break apparently came at Ferney, France, in the spring of 1764, though they did see each other at least one more time a year later.

Upon his return to England, Gibbon published his first book, Essai sur l'Étude de la Littérature in 1761, which produced an initial taste of celebrity and distinguished him, in Paris at least, as a man of letters. From 1759 to 1770, Gibbon served on active duty and in reserve with the South Hampshire militia, his deactivation in December 1762 coinciding with the militia's dispersal at the end of the Seven Years' War. The following year he embarked on the Grand Tour (of continental Europe), which included a visit to Rome. The Memoirs vividly record Gibbon's rapture when he finally neared "the great object of [my] pilgrimage":

I can neither forget nor express the strong emotions which agitated my mind as I first approached and entered the eternal [C]ity. After a sleepless night, I trod, with a lofty step, the ruins of the Forum; each memorable spot where Romulus stood, or Tully spoke, or Caesar fell, was at once present to my eye; and several days of intoxication were lost or enjoyed before I could descend to a cool and minute investigation.

And it was here that Gibbon first conceived the idea of composing a history of the city, later extended to the entire empire, a moment known to history as the "Capitoline vision":

It was at Rome, on the [fifteenth] of October[,] 1764, as I sat musing amidst the ruins of the Capitol, while the bare[-]footed fryars were singing [V]espers in the temple of Jupiter, that the idea of writing the decline and fall of the [C]ity first started to my mind.

His father died in 1770, and after tending to the estate, which was by no means in good condition, there remained quite enough for Gibbon to settle fashionably in London at 7 Bentinck Street, independent of financial concerns. By February 1773 he was writing in earnest, but not without the occasional self-imposed distraction. He took to London society quite easily, joined the better social clubs, including Dr. Johnson's Literary Club, and looked in from time to time on his friend Holroyd in Sussex. He succeeded Oliver Goldsmith at the Royal Academy as 'professor in ancient history' (honorary but prestigious). In late 1774, he was initiated a freemason of the Premier Grand Lodge of England. And, perhaps least productively in that same year, he was returned to the House of Commons for Liskeard, Cornwall, through the intervention of his relative and patron, Edward Eliot. He became the archetypal back-bencher, benignly "mute" and "indifferent," his support of the Whig ministry routinely automatic. Gibbon's indolence in that position, perhaps fully intentional, subtracted little from the progress of his writing.

After several rewrites, with Gibbon "often tempted to throw away the labours of seven years," the first volume of what would become his life's major achievement, The History of the Decline and Fall of the Roman Empire, was published on February 17, 1776. Through 1777, the reading public eagerly consumed three editions for which Gibbon was rewarded handsomely: two-thirds of the profits amounting to approx. £1000. Biographer Leslie Stephen wrote that thereafter, "His fame was as rapid as it has been lasting." And as regards this first volume, "Some warm praise from David Hume overpaid the labour of ten years."

Volumes II and III appeared on March 1, 1781, eventually rising "to a level with the previous volume in general esteem." Volume IV was finished in June 1784; the final two were completed during a second Lausanne sojourn (September 1783 to August 1787) where Gibbon reunited with his friend Deyverdun in leisurely comfort. By early 1787, he was "straining for the goal;" and with great relief the project was finished in June. From the Memoirs:

It was on the ...night of the 27th of June, 1787, between the hours of eleven and twelve, that I wrote the last lines of the last page in a summer-house in my garden. ... I will not dissemble the first emotions of joy on the recovery of my freedom; and perhaps the establishment of my fame. But my pride was soon humbled, and a sober melancholy was spread over my mind by the idea that I had taken my everlasting leave of an old and agreeable friend.

Volumes IV, V, and VI finally reached the press in May 1788, publication having been delayed since March to coincide with a dinner party celebrating Gibbon's 51st birthday (the 8th). Mounting a bandwagon of praise for the later volumes were such contemporary luminaries as Adam Smith, William Robertson, Adam Ferguson, Lord Camden, and Horace Walpole. Smith remarked that Gibbon's triumph had positioned him "at the very head of [Europe's] literary tribe."

The years following Gibbon's completion of The History were filled largely with sorrow and increasing physical discomfort. He had returned to London in late 1787 to oversee the publication process alongside Lord Sheffield, John Baker-Holroyd. With that accomplished, in 1789 it was back to Lausanne only to learn of and be "deeply affected" by the death of Deyverdun, who had willed Gibbon his home, La Grotte. He resided there with little commotion, took in the local society, received a visit from Sheffield in 1791, and "shared the common abhorrence" of the French Revolution. In 1793, word came of Lady Sheffield's death; Gibbon immediately quit Lausanne and set sail to comfort a grieving but composed Sheffield. His health began to fail critically in December, and at the turn of the new year, he was on his last legs.

Gibbon is believed to have suffered from hydrocele testis, a condition which causes the scrotum to swell with fluid in a compartment overlying either testicle. In an age when close-fitting clothes were fashionable, his condition led to a chronic and disfiguring inflammation that left Gibbon a lonely figure. As his condition worsened, he underwent numerous procedures to alleviate the condition, but with no enduring success. In early January, the last of a series of three operations caused an unremitting peritonitis to set in and spread, from which he died. The "English giant of the Enlightenment" finally succumbed at 12:45 pm, January 16, 1794 at age 56. He was buried in the Sheffield family graveyard at the parish church in Fletching, Sussex.