Eighty-five years ago, on 2 June 1924, during a blistering early summer in Chicago, a ravaged courtroom bruiser stepped into the future. Clarence Darrow, with his seamed face and stooped shoulders making him look every one of his 67 years, was America's greatest and most controversial defender of the lost and the damned. But, as he hunched over his desk to write to the secret love of his life, Mary Field Parton, the old lawyer felt breathless.

Earlier that day, Darrow had agreed to represent Nathan Leopold and Richard Loeb, two teenage lovers and the sons of Chicago millionaires, after they confessed to the world's first "thrill-killing" of a 14-year-old boy with whom Loeb had sometimes played tennis. Darrow, the Ohio-born son of an abolitionist father and suffrage-supporting mother, was himself a leading civil libertarian and vehement opponent of the death penalty. In this case, however, he confronted seemingly insurmountable odds; his disturbing and disturbed young clients faced certain execution in what newspapers would soon call the trial of the century.

In agreeing to defend Leopold and Loeb, this brilliant orator who had spent his career battling many personal demons (including a highly damaging accusation of bribing jurors) caught a glimpse of the media-driven world with which we are now so familiar. "I saw a dark vision of the future this morning," Darrow wrote to Parton, a married journalist. "This is all so shocking but, at once, I sense a strange new era. Life will become cheap and tawdry, driven by a lust for sensation and mass stupidity. Man has never been a noble beast but, now, our understanding and mercy will be tested to their limits."

In fact, Darrow was about to plunge into an extraordinary trilogy of cases that would seal his legacy as the most influential trial lawyer in history. Michael Mansfield, the British barrister who defended the Guildford Four and Birmingham Six, and more recently the families of Stephen Lawrence and Jean Charles de Menezes, agrees that, "These three trials were so vast in scope, and so significant in their impact, that Darrow's work remains inspirational. Starting with Leopold and Loeb and going on to the Scopes 'monkey' trial, with its backdrop of evolution, and then defending a black doctor, Ossian Sweet, charged with murder, Darrow swept through a triangle of defining cases in quick succession. In each one he showed a fascinating mix as a man of reason who used such emotion in court. Judges have called my performances histrionic - but it's nothing compared to Darrow."

Far more significant than the glut of Hollywood movies they inspired - from Alfred Hitchcock's Rope to Orson Welles in Compulsion to Spencer Tracey in Inherit the Wind - Darrow's last trio of major cases pushed back courtroom boundaries as he tussled with issues that remain strikingly pertinent. In two dizzying years, he pioneered campaigns against capital punishment, religious fundamentalism (in the form of creationism) and racism, while setting precedents in using psychiatric profiles, expert witnesses and a new form of oratorical showmanship to save his contrasting clients.

The trial of Leopold and Loeb centred on his most passionate cause - overcoming the death penalty - yet the Chicago Sun-Times insisted that he had sold out for "a cool million bucks". (In fact, Darrow's modest fee was decided by the Bar Association). The newspaper branded him a hypocrite who, having always fought for the poor and unfortunate, was now rushing to defend the impossibly rich for a reprehensible murder.

As part of a surreal sexual pact, Leopold and Loeb had randomly chosen the young Bobby Franks as their victim. They lured him into a rental car and, "for the thrill of it", killed him on a suburban side-street. After their arrest, the 19-year-old Leopold stunned reporters by suggesting that "the killing was an experiment.

It is just as easy to justify such a death as it is to justify an entomologist killing a beetle with a pin." Leopold claimed he and Loeb were intellectual supermen galvanised by Friedrich Nietzsche's Beyond Good and Evil. Loeb, 18 and better looking but not as well read, smirked that, "This thing will be the making of me."

He was partially right. The US was fixated by the case - and the public thirst for execution was so intense that individual citizens stated their credentials as hangmen. A pensioner from Michigan offered $100 for the privilege of hanging Leopold and Loeb. "I am 66 years old, but I am game. I have no use for such fiends."

Darrow was undeterred by the personal vitriol. The case perplexed and intrigued him. Unusually, especially for an old man in this more conservative era, he only needed to see how "Babe" Leopold looked yearningly at "Dickie" Loeb to recognise humanity, rather than just fiendish evil, amid their mental disease.

The ensuing trial was dominated by Darrow. First he succeeded in having the evidence heard by a single judge rather than a less easily controlled jury; then he had to make judicial history by persuading the court that mental illness should be regarded as sufficient grounds to commute the death penalty. Psychiatry was then not considered a medical science in legal circles, and Darrow waged battle for two days over the issue, eventually convincing the judge to set a precedent and allow expert witnesses.

Mansfield acknowledges Darrow's groundbreaking work: "With the Tottenham Three [the trio of black men wrongly convicted of murdering PC Keith Blakelock in 1985], we struggled to persuade the court of appeal that judging mental vulnerabilities, as opposed to insanity, should include expert evidence. So it's startling that, in 1924, Darrow opened the door to expert psychiatric evidence. It was a seminal moment."

Darrow, in a closing address spanning an extraordinary three days, produced one of history's most compelling courtroom speeches against capital punishment. On the third day, despite the blue brilliance of the sky outside, he thundered: "Through history you can trace the burnings, the boiling, the drawing and quartering, the hanging of people in England at the crossroads ... I am begging this court not to turn backward to the barbarous past. I am pleading for the future ... when hatred and cruelty will not control our hearts, when we can learn that all life is worth saving; that mercy is the highest attribute of man."

Darrow's eyes moistened when he saw that Judge John Caverly was crying. Newspaper reports the following day refer to them as "silent tears", but they were powerful enough to alter the shape of the judge's twitching mouth. Darrow's strategy, and oratory, had worked. Leopold and Loeb were duly spared the death penalty - and sentenced instead, at Darrow's request, to life imprisonment.

"I've never cried in court and I hope I've never made my juries cry either," says the British barrister John Cooper, who is renowned for his work on the Leah Betts case, and in representing the families of those who died at Deepcut barracks and of those killed in the Hercules and Nimrod disasters in Iraq and Afghanistan. "Darrow, like all great advocates, was a creature of his time. He tapped into the public mind with brilliant oratory. That oratorical art has died because people today are not used to hearing long and florid speeches. The idea that Darrow could speak for six straight hours and hold his audience is staggering.

But in photographs you see hundreds massed outside court to watch him. That wouldn't happen today."

Darrow was hailed by Variety as "America's greatest one-man stage draw" after his next case, the following summer, saw him face down religious fundamentalism in a trial that became just as famous as Leopold and Loeb.

Described as "a duel to the death" between Darrow and the prosecuting attorney (and former Democratic party leader) William Jennings Bryan, the Scopes "monkey" trial began as a publicity stunt. The American Civil Liberties Union hoped to challenge a new law that prohibited the teaching of evolutionary theory in Tennessee, and a local high-school teacher, 24-year-old John Scopes, agreed to be "arrested". The ACLU was less impressed when national hysteria, sparked by the bitter enmity between Bryan and Darrow, swamped the trial. Bryan warned, "If evolution wins, Christianity goes." Darrow responded forcefully: "John Scopes isn't on trial, civilisation is on trial. The prosecution is opening the doors for a reign of bigotry equal to anything in the middle ages."

A furious showdown could only be resolved by a crushing cross-examination from Darrow, who surprised everyone by calling Bryan to the witness stand. He then systematically dismantled the pompous politician, ridiculing his denunciation of scientific fact in favour of biblical allegory with such force that HL Mencken, the celebrated columnist for the Baltimore Evening Sun, could barely contain himself: "This three-time candidate for the presidency came in a hero and he sat down as one of the most tragic asses in American history." At the end of that same week, after the trial fizzled out, Bryan suffered a massive stroke and died. "There's a rumour about town," Scopes wrote, "that 'the old devil Darrow' killed Bryan with his inquisition."

By now, it seemed the whole of the US was captivated by Darrow's courtroom performances. But this was also a nation riven by racial tension and, barely three months later, in October 1925, Darrow again put himself at the centre of controversy by attempting to prevent the apparently inevitable conviction and execution of an eminent black doctor, Ossian Sweet, and 10 other "negroes" accused of murder.

Their crime had been to defend themselves against a Ku Klux Klan-led lynch mob that surrounded the Sweet family's house as soon as they had moved into a white neighbourhood in Detroit. Sweet asked his two brothers and some friends to help protect them and, on the second night, when the mob closed in and a rock smashed a window, Sweet's youngest brother, 21-year-old Henry, fired into the dark. He hit two men, killing one and injuring the other. All 11 in the house were charged with murder.

"The Sweet case," Mansfield says, "carries most resonance for me. It reminds me of the Stephen Lawrence inquest because two decent black families faced similar difficulties. There was extraordinary racism in the Lawrence case - even if it was not as naked as that in Detroit. But I love the way Darrow mixes serious political points with edgy humour. Pure pugilism doesn't work in court because it makes people switch off - he taught us that truth."

Darrow exposed the violent racism of the Sweets' neighbours and a mistrial had to be declared in November 1925, when the all-white jury could not reach a verdict. In the second trial, when Henry Sweet was placed alone in the dock, Darrow produced his greatest performance. He was magisterial when exposing the racism that scarred America, prompting Ossian Sweet to say, "I faced the same mob that had hounded my people through its entire history. I was filled with a peculiar fear, the fear of one who knows the history of my race."

Inspired by such lucidity, Darrow asked the white jurors questions that made them gasp. "If you had a choice," he murmured, "would you lose your eyesight or become coloured? Would you have your leg cut off, or have a black skin?"

In May 1926, during his closing address, Darrow's words rang out as they had done for so many decades in defence of the accused. After seven hours on his feet, he bore down on the jury one last time: "I ask you in the name of progress and the human race to return a verdict of 'not guilty'." But when the foreman, George Small, led the jurors back into court, the swiftness of their deliberations indicated that Darrow had lost. The old attorney's huge head jutted towards the jury box as he waited.

Small paused when asked if they had reached a verdict. "Yes," he said, before crying out the two words that mattered: "Not guilty!"

Ossian Sweet buried his face in his hands while Darrow almost collapsed in exhaustion. The prosecution lawyer Robert Toms rushed to catch him but Darrow, eyes glinting darkly, laughed: "Oh, I'm all right. I've heard that verdict before."

Darrow's Shakespearean battles continue today. Racism may be more subtle than that endured by the Sweets or Stephen Lawrence, but the scars remain raw. And Darrow would have snorted in recognition at the continuing struggle over evolutionary theory. In Tennessee he had asked, "Is it possible this trial is taking place in the 20th century?" And yet, even in our current century, school-board members in Tennessee have campaigned for stickers to be placed across textbooks with the warning that "evolution remains unproven".

Mansfield regards Darrow's work as "a reminder that each generation wages the same war against ignorance and prejudice in a different way. His greatness is that he countered prejudice in every form."

Even more evocatively, Darrow's ghostly figure still conjures up an enduring hope that, even in a dark and reeling world, compassion and reason will finally prevail. "Darrow gave us that belief," Cooper agrees. "You know, if the old devil was around today, I'd love to give him a call for a bit of advice".

• Donald McRae's The Old Devil: Clarence Darrow, The World's Greatest Trial Lawyer is published by Simon & Schuster at £18.99. To order a copy for £17.99 with free UK p&p go to theguardian.com/bookshop or call 0330 333 6846.

Courtroom dramas

Film adaptations of great Darrow cases

Rope (1948)

Directed by Alfred Hitchcock and starring James Stewart, this oblique take on Leopold and Loeb was based on Patrick Hamilton's play of the same name. It now appears rather stilted and dated, but it's still intriguing for the way in which Hitchcock explores Leopold's idea that committing murder would elevate a pair of killers to the realm of Nietzschean supermen.

Compulsion (1959)

Richard Fleischer's film was based on Meyer Levin's "faction" novel. From his prison cell, Leopold attempted to sue Levin and the film's producers, claiming that Levin's version of his story made him feel "physically sick" - because his character agrees to carry out murder so that he might obliterate unwanted homosexual longings inside himself. Orson Welles played Darrow, while Dean Stockwell and Bradford Dillman were Leopold and Loeb.

Inherit the Wind (1960)

A hugely popular but wildly melodramatic version of the Scopes "monkey" trial, Stanley Kramer's Hollywood epic starred Spencer Tracey as Darrow, Fredric March as William Jennings Bryan and Gene Kelly as the acerbic columnist HL Mencken. Nominated for four Oscars, the film now appears terribly overblown. There have since been three TV film versions - with Darrow being played by Melvyn Douglas in 1965, Jason Robards in 1988 and Jack Lemmon in 1999.

Swoon (1992)

Tom Kalin's stylish film stresses the sexual relationship between Leopold and Loeb, and offers a contemporary and largely successful reworking of the story of the strange and stricken young lovers.

Also ...

Michael Haneke's distressing Funny Games (released in Europe in 1997 and again, in a diluted shot-by-shot US remake by the same director, in 2008) and Barbet Schroeder's Murder By Numbers (2002) carry clear allusions to Leopold and Loeb. Meanwhile, in September 2009, in Trevor Nunn's recreation of Inherit the Wind at the Old Vic, Kevin Spacey will play Darrow in the latest theatrical version of the Scopes monkey trial.