In 1818 Mary Shelley published Frankenstein, the story of a man who trespasses on God’s turf by crafting a new form of life. She took its epigraph from Book X of John Milton’s Paradise Lost, when Adam rages at God like a teenager who didn’t ask to be born. Shelley returned to Milton for 1826’s The Last Man, a grim, grief-sodden read about an annihilating pandemic: “Let no man seek / Henceforth to be foretold what shall befall / Him or his children.” One novel describes the creation of life, the other its destruction, and both open with Paradise Lost.

It is no surprise that Milton’s epic figured in the genesis of science fiction. Orlando Reade suggests that it “might be the most influential poem in English”, frequently stripped for parts. In relatively recent years, it has furnished the titles of Philip Pullman’s His Dark Materials trilogy and Nick Cave’s Red Right Hand, influenced the collapse of the candy-pink Eden in Greta Gerwig’s Barbie and undergirded the series three finale of The Good Place, whose title, Pandemonium, is one of many Miltonic neologisms. As a young man, Milton dreamed of creating an epic poem “so written to aftertimes, as they should not willingly let it die”. That hope was fulfilled, in ways he could not have comprehended.

It is 350 years since Milton died, shortly after revising his masterpiece (the first version was published in 1667). Writing it was a heroic feat. Between 1652 and 1660, he had lost a son, a daughter, two wives, his sight, his job, his political project and almost his life. As a Cromwellian propagandist who had endorsed regicide, he was lucky to survive the Restoration. Yet in the aftermath of total defeat he still had enough energy and self-belief to not only radically expand the scope of English poetry but rewrite Genesis to tell his own story of mankind, the universe, Heaven and Hell. Milton credited a celestial muse and it’s enough to make even an atheist wonder about divine intervention. He received an advance of just £5 (less than £1,000 today) but within decades Milton was stationed beside Shakespeare at the summit of English literature.

It is Paradise Lost’s afterlife as a political document, rather than a work of art, that most interests Reade. As he ably demonstrates, writers and political activists have been raiding the text for inspiration for centuries, coming to often incompatible conclusions. Lively and humane, Reade is the friendliest of academics. Like many an English literature undergraduate, he was initially daunted by Paradise Lost (“a mountain … whose slopes are scattered with bodies”) but came to adore it while teaching poetry to prisoners, and he wants you to love it, too.

Each of the dozen chapters summarises the corresponding book of Paradise Lost and profiles a famous reader of the poem, from Thomas Jefferson and George Eliot to Max Weber and Hannah Arendt, with mixed results. The strength of the connective tissue varies and the topical analogies (Satan as tech CEO?) get a little strained. To claim that Blade Runner is “the most influential cinematic version of Paradise Lost” may be a juicy conversation-starter but to call Milton the “unacknowledged legislator … of mass incarceration” is a stretch. Still, Reade’s enthusiasm and curiosity are winning.

Milton promised to “justify the ways of God to men”, by which he meant explain how a deity that is both benevolent and omnipotent could permit so much evil and suffering. Well, he failed. And Paradise Lost is great precisely because it fails as propaganda. Written in an age of murderous polarisation, it writhes with contradictions, particularly concerning the tension between liberty and authority. As the critic William Empson observed, “the poem is not good in spite of, but especially because of, its moral confusions … I think it horrible and wonderful.”

Put briefly, Satan aspires to corrupt humanity to avenge his defeat in the war in Heaven, and God empowers his efforts in order to test Adam and Eve’s judgment: “Sufficient to have stood, though free to fall.” Milton may not have intended to equate God with Charles I, or Satan with Cromwell, but his revolutionary sympathies surely explain why Satan gets most of the best lines: “Better to reign in Hell, than serve in Heav’n” is a slogan for the ages. In the Bible the Devil is merely an antagonist – God’s negative image – but Milton gave him a charismatic personality, and the majesty of opposition against the odds. William Blake famously observed that the poet was “of the Devil’s party without knowing it”. Milton’s God, by contrast, is a chilly authoritarian, hard to love and passionately denounced by both his enemies and his creations. Empson remarked that the deity was “astonishingly like Uncle Joe Stalin”.

Every era finds a different use for Paradise Lost. The Romantics took it primarily as a rebel yell. Even though Satan degenerates towards petty tyranny and ultimate humiliation, Percy Shelley saw him as a glamorous Promethean hero and adopted the line “Awake, arise, or be for ever fall’n” for 1812’s Declaration of Rights. American revolutionaries such as Jefferson and Paine, less keen to be aligned with the Devil, preferred to quote the stirring rhetoric while smudging its origins. “By 1776,” Reade writes, “Milton had become American.” But what kind of American? Slavery is one of Reade’s core themes. Paradise Lost was embraced by abolitionists such as James Redpath (“man over men / He made not lord”) as well as the Mistick Krewe of Comus, diehard New Orleans segregationists who twisted it into a justification of white supremacy.

Not all radicals identified with Satan’s defiance. When Malcolm X read Paradise Lost in Norfolk Prison Colony in 1948, Satan reminded him of Yakub, the evil scientist who, according to the Nation of Islam, created white people. Conservatives certainly did not. Edmund Burke found it “dark, uncertain, confused, terrible”. Jordan Peterson sees Satan as a prophecy of Enlightenment arrogance, leading to the gulag. (Everything leads to the gulag with Peterson.) During the Arab spring, an Assadist Syrian newspaper cited Paradise Lost as proof that all revolutions fail. Some of Reade’s subjects performed fascinating U-turns: CLR James initially dismissed Milton as a proto-Stalinist before deciding that the poem was in fact a vital warning about insurgents turned despots.

People love Paradise Lost for divergent reasons. Sometimes they love and hate it simultaneously. Goethe thought the poetry “majestic” but the subject “detestable”. Even the modernists, who liked to use Paradise Lost as a punchbag, were conflicted. Virginia Woolf considered it cold-hearted and misogynistic yet still “the essence, of which all other poetry is the dilution”, while TS Eliot scorned it even as he pillaged it in The Waste Land. Milton was literature’s looming patriarch, who had to be admired even when he was loathed.

Such ambivalence is the most appropriate response to Milton’s endless contradictions. Reade’s more emphatic claims undermine his pluralistic conclusion that Paradise Lost’s strength is the potency of its competing arguments, in line with Milton’s defence of free speech as the surest way to reach the truth. Yet he is confident that Milton’s heart lay with neither God nor Satan but Adam and Eve, who have the freedom to make catastrophic mistakes and, the world all before them, to decide how to live with the consequences. The ending is a new beginning.

• What in Me Is Dark: The Revolutionary Life of Paradise Lost by Orlando Reade is published by Jonathan Cape (£22). To support the Guardian and the Observer go to guardianbookshop.com. Delivery charges may apply.