Symonds was born at Bristol. His father, the senior John Addington Symonds, MD (1807—1871), was the author of an essay on Criminal Responsibility (1869), The Principles of Beauty (1857) and Sleep and Dreams (2nd ed., 1857).

Considered delicate, the younger Symonds did not take part in games while at Harrow School from May 1854 and showed no particular promise as a scholar.

In January 1858 Symonds received a letter from Alfred Pretor (1840—1908), a friend of his, in which Pretor told him he was having an affair with their headmaster, Charles John Vaughan. Symonds was shocked and disgusted, feelings complicated by his growing awareness of his own homosexuality. He didn't mention the incident for more than a year until, in 1859, he blurted out the whole story to John Conington, the Latin professor at Oxford. Conington approved of romantic relationships between men and boys, having earlier given Symonds a copy of Ionica, a collection of thinly disguised homoerotic verse by William Johnson Cory, the influential Eton Master and advocate of pederastic pedagogy. Nonetheless, Conington encouraged Symonds to tell his father, who subsequently forced Vaughan to resign. Pretor was disgusted with Symonds' part in the whole affair, and never spoke to him again.

In 1858 Symonds proceeded to Balliol College, Oxford as a commoner but was elected to an exhibition in the following year. In spring of that same year he had fallen in love with Willie Dyer (William Fear Dyer 1843-1905), a Bristol choirboy three years younger than himself. They engaged in a passionate but chaste love affair that lasted one year, being broken up by Symond's father. Their friendship continued for several years afterwards, until at least 1864. Dyer became organist & choirmaster of St Nicholas' Church, Bristol.

At Oxford, Symonds began to reveal his academic ability. In 1860 he took a first in Mods and won the Newdigate prize with a poem on "The Escorial"; in 1862 he obtained a first in Literae Humaniores and in the following year was winner of the Chancellor's English Essay.

In 1862 he had been elected to an open fellowship at the conservative Magdalen, where he would be the focus of a scandal. He made friends with a C.G.H. Shorting, whom he took as a private pupil. However, when Symonds refused to help Shorting gain admission to Magdalen, Shorting sent a letter to school officials alleging "that I [Symonds] had supported him in his pursuit of the chorister Walter Thomas Goolden (1848-1901), that I shared his habits and was bent on the same path." Although Symonds was officially cleared of any wrongdoing, the stress of the ordeal precipitated a breakdown in health. Shortly thereafter he left for Switzerland.

There he met Janet Catherine North. After a romantic betrothal in the mountains, he married her at Hastings on 10 November 1864. They settled in London and had four daughters, Janet (born 1865), Charlotte (born 1867), Margaret (born 1869) and Katharine, later Dame Katharine Furse (born 1875). Symonds hoped to study law, but his health again broke down and forced him to travel. Returning to Clifton, he lectured there, both at the college and to ladies' schools; the results can be seen in his Introduction to the Study of Dante (1872) and his Studies of the Greek Poets (1873—1876).

While in Clifton in 1868 he met and fell in love with Norman Moor, a schoolboy about to go up to Oxford, who also became his pupil. Their pederastic affair, erotic and sensual but kept short of coitus, lasted four years. According to his diary of 28 January 1870, "I stripped him naked and fed sight, touch and mouth on these things." The relationship occupied a good part of his time (on one occasion he left his family and traveled to Italy and Switzerland with the boy) and inspired his most productive period of writing poetry, published in 1880 as New and Old: A Volume of Verse.

Meanwhile he was occupied with his major work, Renaissance in Italy, which appeared in seven volumes at intervals between 1875 and 1886. The Renaissance had been the subject of Symonds' prize essay at Oxford, and this had aroused a desire to produce a more complete picture of the reawakening of art and literature in Europe. His work, however, was again interrupted by illness, this time more serious. In 1877 his life was in danger, and the recovery he made at Davos-Platz led to a belief that this was the only place where he was likely to be able to enjoy life.

He practically made his home at Davos. A charming picture of his life there is drawn in Our Life in the Swiss Highlands (1891). Symonds became a citizen of the town; he took part in its municipal business, made friends with the peasants and shared their interests. There he wrote most of his books: biographies of Shelley (1878), Philip Sidney (1886), Ben Jonson (1886) and Michelangelo (1893), several volumes of poetry and essays, and a translation of the Autobiography of Benvenuto Cellini (1887).

There, too, he completed his study of the Renaissance, the work for which he is mainly remembered. He was feverishly active throughout his life. The amount of work he achieved was remarkable, considering his poor health. He had a passion for Italy and for many years resided during the autumn in the house of his friend, Horatio F Brown, on the Zattere, in Venice. He died in Rome and was buried close to Shelley.

He left his papers and his autobiography in the hands of Brown, who wrote an expurgated biography in 1895, which Edmund Gosse further stripped of homoerotic content before its publication. In 1926, upon coming into the possession of Symonds' papers, Gosse proceeded to burn everything except the memoirs, to the dismay of Symonds' granddaughter. Two works, a volume of essays, In the Key of Blue, and a monograph on Walt Whitman, were published in the year of his death. His activity was unbroken to the last.

In life Symonds was morbidly introspective, but with a capacity for action. Robert Louis Stevenson described him, in the Opalstein of Talks and Talkers, as "the best of talkers, singing the praises of the earth and the arts, flowers and jewels, wine and music, in a moonlight, serenading manner, as to the light guitar." Beneath his good fellowship lurked a haunting melancholy. He was tormented by the riddles of existence.

This side of his nature is revealed in his gnomic poetry, and particularly in the sonnets of his Animi Figura (1882), where he has portrayed his own character with great subtlety. His poetry is perhaps rather that of the student than of the inspired singer, but it has moments of deep thought and emotion.

It is, indeed, in passages and extracts that Symonds appears at his best. Rich in description, full of "purple patches," his work lacks the harmony and unity essential to the conduct of philosophical argument. His translations are among the finest in the language; here his subject was found for him, and he was able to lavish on it the wealth of colour and quick sympathy which were his characteristics.

While the taboos of Victorian England prevented Symonds from speaking openly about homosexuality, his works published for a general audience contained strong implications and some of the first direct references to male-male sexual love in English literature. For example, in "The Meeting of David and Jonathan", from 1878, Jonathan takes David "In his arms of strength / [and] in that kiss / Soul into soul was knit and bliss to bliss".

The same year, his translations of Michelangelo's sonnets to the painter's beloved Tommaso Cavalieri return the male pronouns which had been made heterosexual by previous editors into female pronouns. By the end of his life, Symonds' homosexuality had become an open secret in Victorian literary and cultural circles.

Simultaneously to these widely available works, Symonds was writing, privately publishing and distributing more candid writings about homosexuality. As well as a large number of poems written throughout the 1860s and 1870s, Symonds wrote one of the first essays in defense of homosexuality in the English language, A Problem in Greek Ethics, in 1883. A follow-up essay from 1891, A Problem in Modern Ethics, includes proposals for reforming anti-homosexual legislation.

These essays were widely read by an underground of homosexual writers and continued to be secretly published and distributed decades after his death. Some of his other personal writings and letters were finally published in the late twentieth century, and are of great interest to historians for the candid descriptions of an "unspeakable" sexual culture which existed against the "social law" of his time that "regarded this love as abominable and unnatural."

In particular, Symonds' memoirs, written over a four year period, from 1889 to 1893, form the earliest known self-conscious homosexual autobiography. In addition to realizing his own homosexuality, Symonds' daughter, Madge Vaughan, was probably writer Virginia Woolf's first same-sex crush, though there is no evidence that the feeling was mutual. Woolf was the cousin of her husband William Wyamar Vaughan. Another daughter, Charlotte Symonds, married the classicist Walter Leaf. Henry James used some details of Symonds' life, especially the relationship between him and his wife, as the starting-point for the short story The Author of Beltraffio (1884).

Over a century after Symonds' death his first work on homosexuality Soldier Love and Related Matter was finally published by Andrew Dakyns (grandson of Henry Graham Dakyns), Eastbourne, E. Sussex, England 2007. Soldier Love, or Soldatenliebe since it was limited to a German edition. Symonds' English text is lost. This translation and edition by Dakyns is the only version ever to appear in the author's own language.