Both Henry and his twin Thomas were schooled locally by the rector of Llangattock , the Rev. Matthew Herbert. This occupied six years preceding their attendance at Jesus College, Oxford, England in 1638. However, around 1640, Vaughan's family influenced him to pursue a career in law to the abandonment of an Oxford degree.

As the Civil War developed, he was recalled home from London, initially to serve as a secretary to Sir Marmaduke Lloyd, a chief justice on the Brecknockshire circuit and staunch royalist. Military service interrupted his study of the law and, upon his return, Vaughan began to practise medicine. By 1646, he had married Catherine Wise with whom he reared a son, Thomas, and three daughters, Lucy, Frances, and Catherine. After his first wife's death, he married her sister, Elizabeth.

Vaughan took his literary inspiration from his native environment and chose the descriptive name "Silurist," derived from his homage to the Silures, the Celtic tribe of pre-Roman south Wales which strongly resisted the Romans. This name is a reflection of the deep love Vaughan felt towards the Welsh mountains of his home in what is now part of the Brecon Beacons National Park and the River Usk valley where he spent most of his early life and professional life.

By 1647 Henry Vaughan, with his wife and children, had chosen life in the country. This is the setting in which Vaughan wrote Olor Iscanus, the (Swan of Usk). However, this collection was not published until 1651, more than three years after it was written. It is believed that there was great crisis in Vaughan's life between the authorship and publication of Olor Iscanus. During these years, his grandfather William Vaughan died and he was evicted from his living in Llansantffraed. Vaughan later decried the publication, having "long ago condemned these poems to obscurity".

Olor Iscanus is filled with odd words and similes that beg for attention despite its dark and morbid cognitive appeal. This work is founded on crises felt in Vaughan's homeland, Brecknockshire. During the Civil War, there was never a major battle fought on the ground of Brecknockshire, but the effects of the war were deeply felt by Vaughan and his surrounding community. The Puritan Parliament visited misfortune on the community, ejecting many of their foes, the Anglicans and Royalists. This was an obvious source of misfortune for Vaughan, who also lost his home at that time.

There is a distinct difference between the atmosphere Vaughan attempts to convey in this work and in his most famous work, Silex Scintillans. Olor Iscanus is a direct representation of a specific period in Vaughan's life, which emphasizes other secular writers and provides allusions to debt and happy living. A fervent topic of Vaughan throughout these poems is the Civil War and reveals Vaughan's somewhat paradoxical thinking that, in the end, gives no clear conclusion to the question of his participation in the Civil War. Vaughan states his complete satisfaction of being clean on "innocent blood" but also provides what seem to be eyewitness accounts of battles and his own "soldiery". Although Vaughan is thought to have been a royalist, these poems express contempt for all current authority and a lack of zeal for the royalist cause. His poems generally reflect a sense of severe decline, which possibly means that Vaughan lamented the effects of the war on the monarchy and society. His short poem "The Timber", ostensibly about a dead tree, concludes "thy strange resentment after death / Means only those who broke - in life - thy peace."

The period shortly preceding the publication of Henry Vaughan's Silex Scintillans marked an important period of his life. Certain indications in the first volume and explicit statements made in the preface to the second volume of Silex Scintillans suggest that Vaughan suffered a prolonged sickness that inflicted much pain. Vaughan interprets this experience to be an encounter with death and a wake-up call to his "misspent youth". Vaughan believes he is spared to make amends and start a new course not only in his life but in the literature he would produce. Vaughan himself describes his previous work as foul and a contribution to "corrupt literature". Perhaps the most notable mark of Vaughan's conversion is how much it is credited to George Herbert. Vaughan claims that he is the least of Herbert's many "pious converts". It is during this period of Vaughan's life, around 1650, that he adopts the saying "moriendo, revixi", meaning "by dying, I gain new life".

It was not until Vaughan's conversion and the writing of Silex Scintillans that he received significant acclaim. He was greatly indebted to George Herbert, who provided a model for Vaughan's newly founded spiritual life and literary career, in which he displayed "spiritual quickening and the gift of gracious feeling" derived from Herbert.

Archbishop Trench has proposed that "As a divine Vaughan may be inferior [to Herbert], but as a poet he is certainly superior". Critics praise Vaughan's use of literary elements. Vaughan's use of monosyllables, long-drawn alliterations and his ability to compel the reader places Vaughan as "more than the equal of George Herbert". Yet others say that the two are not even comparable, because Herbert is in fact the Master. While these critics admit that Henry Vaughan's use of words can be superior to Herbert's, they believe his poetry is, in fact, worse. Herbert's profundity as well as consistency are said to be the key to his superiority.

While the superiority or inferiority of Vaughan and Herbert is a question with no distinct answer, one cannot deny that Vaughan would have never written the way he did without Herbert's direction. The explicit spiritual influence of Herbert on Henry Vaughan is undeniable. The preface to Vaughan's Silex Scintillans does all but proclaim this influence. The prose of Vaughan exemplifies this as well. For instance, The Temple, by Herbert, is often seen as the inspiration and blueprints through which Vaughan modelled to create his work. Silex Scintillans is most often classed with this collection of Herbert's. Silex Scintillans borrows the same themes, experience, and beliefs as The Temple. Herbert's influence is evident both in the shape and spirituality of Vaughan's poetry. For example, the opening to Vaughan's poem 'Unprofitableness':

How rich, O Lord! How fresh thy visits are!

is reminiscent of Herbert's 'The Flower':

How fresh, O Lord, how sweet and clean

Are thy returns! ev'n as the flowers in spring

Another work of Vaughan's that clearly parallels George Herbert is Mount of Olives, e.g., the passage, Let sensual natures judge as they please, but for my part, I shall hold it no paradoxe to affirme, there are no pleasures in the world. Some coloured griefes of blushing woes there are, which look as clear as if they were true complexions; but it is very sad and tyred truth, that they are but painted. This echoes Herbert's Rose:

In this world of sugar's lies,

And to use a larger measure

Than my strict yet welcome size.

First, there is no pleasure here:

Coloure'd griefs indeed there are,

Blushing woes that look as clear,

As if they could beauty spare.

Critics have complained that Vaughan is enslaved to Herbert's works, using similar "little tricks" such as abrupt introductions and whimsical titles as a framework for his own work, and that he "failed to learn" from Herbert. Vaughan carried an inability to know his limits and focused more on the intensity of the poem, meanwhile losing the attention of his audience.

However, Alexander Grosart denies that Henry Vaughan was solely an imitator of George Herbert (Grosart, 3). There are moments in Vaughan's writings where the reader can identify Vaughan's true self, rather than an imitation of Herbert. In such passages Vaughan is seen to demonstrate naturalness, immediacy, and ability to relate the concrete through poetry. In some instances, Vaughan derives observations from Herbert's language that are distinctly his own. It is as if Vaughan takes proprietorship of some of Herbert's work, yet makes it completely unique to himself.Henry Vaughan takes another step away from George Herbert in the manner to which he presents his poetry to the reader. George Herbert in The Temple, which is most often the source of comparison between the two writers, lays down explicit instructions on the reading of his work. This contrasts with the attitude of Vaughan, who considered the experience of reading as the best guide to his meanings. He promoted no special method of reading his works .

In these times he shows himself different from any other poet. Much of his distinction derives from an apparent lack of sympathy with the world around him. His aloof appeal to his surroundings detaches him and encourages his love of nature and mysticism, which in turn influenced other later poets, Wordsworth among others. Vaughan's mind thinks in terms of a physical and spiritual world and the obscure relation between the two. Vaughan's mind often moved to original, unfamiliar, and remote places, and this reflected in his poetry. He was loyal to the themes of the Anglican Church and religious festivals, but found his true voice in the more mystical themes of eternity, communion with the dead, nature, and childhood.A poet of revelation who uses the Bible,Nature and his own experience to illustrate his vision of eternity. .Vaughan's poetry has a particularly modern sound.

Alliteration (conspicuous in Welsh poetry)is more extensively used by Vaughan than most of his contemporaries writing English verse,noticeably in the opening to The Water-fall .

Vaughan elaborated on personal loss in two well-known poems, "The World" and "They Are All Gone in the World of Light." Another poem, "The Retreat," combines the theme of loss with the corruption of childhood, which is yet another consistent theme of Vaughan's. Vaughan's newfound personal voice and persona are seen as the result of the death of a younger brother.

This is an example of an especially beautiful fragment of one of his poems entitled "The World:"

I saw eternity the other night

Like a great ring of pure and endless light,

All calm as it was bright,

And round beneath it time in hours, days, years,

Driven by the spheres,

Like a vast shadow moved in which the world

And all her train were hurled.

As is the case with many great writers and poets, Henry Vaughan was acclaimed less during his lifetime than after his death on April 23, 1695, aged 74. He is buried in the churchyard of St Bridget's, Llansantffraed, Powys. He is recognised "as another example of a poet who can write both graceful and effective prose" and influenced the work of poets such as Wordsworth, Tennyson and Siegfried Sassoon. The American science fiction writer Philip K. Dick even named Vaughan as a key influence.