He was born on 9 February 1853, of the Jameson family of Edinburgh, Scotland, the son of Robert William Jameson (1805 – 1868), a Writer to the Signet, and Christian Pringle, daughter of Major General Pringle of Symington. Robert William and Christian Jameson had twelve children, of whom Leander Starr was the youngest, born at Stranraer, Galloway, in the south-west of Scotland, great-nephew of Professor Robert Jameson, Regius Professor of Natural History at the University of Edinburgh. Fort's biography of Jameson notes that Starr's '...chief Gamaliel, however, was a Professor Grant, a man of advanced age, who had been a pupil of his great-uncle, the Professor of Natural History at Edinburgh.'

Leander Starr Jameson's somewhat unusual name resulted from the fact that his father Robert William Jameson had been rescued from drowning on the morning of his birth by an American traveller, who fished him out of a canal or river with steep banks into which William had fallen while on a walk awaiting the birth of his son. The kindly stranger named "Leander Starr" was promptly made a godfather of the baby, who was named after him. His father, Robert William, started his career as an advocate in Edinburgh, and was Writer to the Signet, before becoming a playwright, published poet and editor of the Wigtownshire Free Press.

A radical and reformist, Robert William Jameson was the author of the dramatic poem Nimrod (1848) and Timoleon, a tragedy in five acts informed by the anti-slavery movement. Timoleon was performed at the Adelphi Theatre in Edinburgh in 1852, and ran to a second edition. In due course, the Jameson family moved to London, England, living in Chelsea and Kensington. Leander Starr Jameson went to the Godolphin School in Hammersmith, where he did well in both lessons and games prior to his university education.

L.S. Jameson was educated for the medical profession at University College Hospital, London, for which he passed his entrance examinations in January, 1870. He distinguished himself as a medical student, becoming a Gold Medallist in materia medica. After qualifying as a doctor, he was made Resident Medical Officer at University College Hospital (M.R.C.S. 1875; M.D. 1877).

After acting as house physician, house surgeon and demonstrator of anatomy, and showing promise of a successful professional career in London, his health broke down from overwork in 1878, and he went out to South Africa and settled down in practice at Kimberley. There he rapidly acquired a great reputation as a medical man, and, besides numbering President Kruger and the Matabele chief Lobengula among his patients, came much into contact with Cecil Rhodes.

Jameson was for some time the inDuna of the Matabele king's favourite regiment, the Imbeza. Lobengula expressed his delight with Jameson's successful medical treatment of his gout by honouring him with the rare status of inDuna. Although Jameson was a white man, he underwent the initiation ceremonies linked with this honour. Jameson's status as an inDuna gave him advantages, and in 1888 he successfully exerted his influence with Lobengula to induce the chieftain to grant the concessions to the agents of Rhodes which led to the formation of the British South Africa Company; and when the company proceeded to open up Mashonaland, Jameson abandoned his medical practice and joined the pioneer expedition of 1890. From this time his fortunes were bound up with Rhodes' schemes in the north. Immediately after the pioneer column had occupied Mashonaland, Jameson, with F.C. Selous and A.R. Colquhoun, went east to Manicaland and was instrumental in securing the greater part of the country, to which Portugal was laying claim, for the Chartered Company. In 1891 Jameson succeeded Colquhoun as Administrator of Mashonaland. In 1893, Jameson was a key figure in the First Matabele War and involved in incidents that led to the massacre of the Shangani Patrol. Jameson's character seems to have inspired a degree of devotion from his contemporaries. Elizabeth Longford writes of him, "Whatever one felt about him or his projects when he was not there, one could not help falling for the man in his presence.... People attached themselves to Jameson with extraordinary fervour, the more extraordinary because he made no effort to feed it. He affected an attitude of tough cynicism towards life, literature and any articulate form of idealism, particularly towards the hero-worship which he himself excited ... When he died The Times estimated that his astonishing personal hold over his followers had been equalled only by that of Parnell, the Irish patriot." Longford also notes that Rudyard Kipling wrote the poem 'If' with Leander Starr Jameson in mind as an inspiration for the characteristics he recommended young people to live by (notably Kipling's son, to whom the poem is addressed in the last lines). Longford writes, "Jameson was later to be the inspiration and hero of Rudyard Kipling's poem, 'If'...". Direct evidence that the poem 'If' was written about Jameson is available also in Rudyard Kipling's autobiography in which Kipling writes that "If--" was "drawn from Jameson's character."

As reported below, in 1895, Jameson led about 500 of his countrymen in what became known as The Jameson Raid against the Boers in southern Africa. The Jameson Raid was later cited by Winston Churchill as a major factor in bringing about the Boer War of 1899 to 1902. But the story as recounted in Britain was quite different. The British defeat was interpreted as a victory and Jameson was portrayed as a daring hero. The poem celebrates heroism, dignity, stoicism and courage in the face of the disaster of the failed Jameson Raid, for which he was wrongfully made a scapegoat.

Jameson's persuasive character, what became known later as 'the Jameson charm', was described in some detail by G.Seymour Fort (1918), who writes of his restless, logical and sagacious temperament in this way:

"... It was not his wont to talk at length, nor was he, unless exceptionally interested, a good listener. He was so logical and so quick to grasp a situation, that he would often cut short exposition by some forcible remark or personal raillery that would all too often quite disconcert the speaker.

Despite his adventurous career, mere reminiscences obviously bored him; he was always for movement, for some betterment of present or future conditions, and in discussion he was a master of the art of persuasion, unconsciously creating in those around him a latent desire to follow, if he would lead. The source of such persuasive influence eludes analysis, and, like the mystery of leadership, is probably more psychic than mental. In this latter respect, Jameson was splendidly equipped; he had greater power of concentration, of logical reasoning, and of rapid diagnosis, while on his lighter side he was brilliant in repartee and in the exercise of a badinage that was both cynical and personal...

.... He wrapped himself in cynicism as with a cloak, not only to protect himself against his own quick human sympathy, but to conceal the austere standard of duty and honour that he always set to himself. He was ever trying to hide from his friends his real attitude towards life, and the high estimate he placed upon accepted ethical values... He was essentially a patriot who sought for himself neither wealth, nor power, nor fame, nor leisure, nor even an easy anchorage for reflection. The wide sphere of his work and achievements, and the accepted dominion of his personality and his influence were both based upon his adherence to the principle of always subordinating personal considerations to the work in hand, upon the loyalty of his service to big ideals. His whole life seems to illustrate the truth of the saying that in self-regard and self-centredness there is no profit, and that only in sacrificing himself for impersonal aims can a man save his soul and benefit his fellow men."

In November 1895, a piece of territory of strategic importance, the Pitsani Strip, part of the Bechuanaland Protectorate and bordering the Transvaal, was ceded to the British South Africa Company by the Colonial Office, overtly for the protection of a railway running through the territory. Cecil Rhodes, the Prime Minister of the Cape Colony and managing director of the Company was eager to bring South Africa under British dominion, and encouraged the disenfranchised Uitlanders of the Boer republics to resist Afrikaner domination. Rhodes hoped that the intervention of the Company's private army could spark an Uitlander uprising, leading to the overthrow of the Transvaal government. Rhodes' forces were assembled in the Pitsani Strip for this purpose. Joseph Chamberlain informed Salisbury on Boxing Day that an uprising was expected, and was aware that an invasion would be launched, but was not sure when. The subsequent Jameson Raid was a debacle, leading to the invading force's surrender. Chamberlain, at Highbury, received a secret telegram from the Colonial Office on 31 December informing him of the beginning of the Raid.

In 1895, Jameson assembled a private army outside the Transvaal in preparation for the violent overthrow of the Boer government. The idea was to foment unrest among foreign workers (Uitlanders) in the territory, and use the outbreak of open revolt as an excuse to invade and annex the territory. Growing impatient, Jameson launched the Jameson Raid in December 1895, and managed to push within twenty miles of Johannesburg before superior Boer forces compelled him and his men to surrender.

Sympathetic to the ultimate goals of the Raid, Chamberlain was uncomfortable with the timing of the invasion and remarked that "if this succeeds it will ruin me. I'm going up to London to crush it". He swiftly travelled by train to the Colonial Office, ordering Sir Hercules Robinson, Governor-General of the Cape Colony, to repudiate the actions of Jameson and warned Rhodes that the Company's Charter would be in danger if it were discovered that the Cape Prime Minister was involved in the Raid. The prisoners were returned to London for trial, and the Transvaal government received considerable compensation from the Company. Jameson was tried in England for leading the raid; during that time he was lionized by the press and London society.

The Jameson Raiders arrived in England at the end of February, 1896 to face trial. There were some months of investigations initially held at Bow Street, following which the 'trial at bar' (a legal procedure reserved only for very important cases) began on June 20, 1896, at the High Court of Judicature. The trial lasted seven days, following which Dr Jameson was 'found guilty and sentenced to imprisonment as a first-class misdemeanant for fifteen months. He was, however, released from Holloway in the following Dec on account of illness.'

During the trial of Jameson, Rhodes' solicitor, Bourchier Hawksley, refused to produce cablegrams that had passed between Rhodes and his agents in London during November and December 1895. According to Hawksley, these demonstrated that the Colonial Office 'influenced the actions of those in South Africa' who embarked on the Raid, and even that Chamberlain had transferred control of the Pitsani Strip to facilitate an invasion. Nine days before the Raid, Chamberlain had asked his Assistant Under-Secretary to encourage Rhodes to 'Hurry Up' because of the deteriorating Venezuelan situation. Jameson was sentenced to fifteen months in jail, but was soon pardoned. In June 1896, Chamberlain offered his resignation to Salisbury, having shown the Prime Minister one or more of the cablegrams implicating him in the Raid's planning. Salisbury refused to accept the offer, possibly reluctant to lose the government's most popular figure. Salisbury reacted aggressively in support of Chamberlain, supporting the Colonial Secretary's threat to withdraw the Company's charter if the cablegrams were revealed. Accordingly, Rhodes refused to reveal the cablegrams, and as no evidence was produced showing that Chamberlain was complicit in the Raid's planning, the Select Committee appointed to investigate the events surrounding the Raid had no choice but to absolve Chamberlain of all responsibility.

Jameson had been Administrator General for Matabeleland at the time of the Raid and his intrusion into Transvaal depleted Matabeleland of many of its troops and left the whole territory vulnerable. Seizing on this weakness, and a discontent with the British South Africa Company, the Matabele revolted in March 1896 in what is now celebrated in Zimbabwe as the First War of Independence – the Second Matabele War. Hundreds of white settlers were killed within the first few weeks and many more would die over the next year and a half at the hands of both the Matabele and the Shona. With few troops to support them, the settlers had to quickly build a laager in the centre of Bulawayo on their own. Against over 50,000 Matabele held up in their stronghold of the Matobo Hills as the settlers mounted patrols under such legendary figures as Burnham, Baden-Powell, and Selous. After the Matabele laid down their arms, the war continued until October 1897 in Mashonaland.

Despite the Raid, Jameson had a successful political life following the invasion, receiving many honours in later life. In 1903 Jameson came forward as the leader of the Progressive (British) party in the Cape Colony. When the party was successful he became Prime Minister of the Cape Colony from 1904 to 1908. He served as the leader of the Unionist Party (South Africa) from its founding in 1910 until 1912. Jameson was created a baronet in 1911 and returned to England in 1912.

According to Rudyard Kipling, his famous poem "If— " was written in celebration of Leander Starr Jameson's personal qualities at overcoming the difficulties of the Raid, for which he largely took the blame, though Joseph Chamberlain, British colonial secretary of the day, was, according to some historians, implicated in the events of the raid. Jameson is buried at Malindidzimu Hill l or World's View, a granite hill in the Matobo National Park 40 km south of Bulawayo. It was designated by Cecil Rhodes as the resting place for those who served Great Britain well in Africa. Rhodes is also buried there.

Jameson died in the afternoon of Monday, November 26, 1917 in the City of London. His body was laid in a vault at Kensal Green Cemetery on 29 November, 1917, where it remained until the end of the First World War.

Ian Colvin (1923) writes that Jameson's body was then: "...carried to Rhodesia and on May 22, 1920, laid in a grave cut in the granite on the top of the mountain which Rhodes had called The View of the World, close beside the grave of his friend. 'Thy firmness makes my circle just, And makes me end where I begun.' There on the summit those two lie together."

To this day, the events surrounding Jameson's involvement in the Jameson Raid, being in general somewhat out of character with his prior history, the rest of his life and successful later political career, remain something of an enigma to historians. In 2002, The Van Riebeck Society published Sir Graham Bower’s Secret History of the Jameson Raid and the South African Crisis, 1895-1902, adding to growing historical evidence that the imprisonment and judgement upon the Raiders at the time of their trial was an underhanded move by the British government, a result of political manoeuvres by Joseph Chamberlain and his staff to hide his own involvement and knowledge of the Raid. In his review of Sir Graham Bower’s Secret History ...Alan Cousins, notes that, 'A number of major themes and concerns emerge' from Bower's history, '... perhaps the most poignant being Bower’s accounts of his being made a scapegoat in the aftermath of the raid: "since a scapegoat was wanted I was willing to serve my country in that capacity".' Cousins notes of Bower that 'a very clear sense of his rigid code of honour is plain, and a conviction that not only unity, peace and happiness in South Africa, but also the peace of Europe would be endangered if he told the truth. He believed that, as he had given Rhodes his word not to divulge certain private conversations, he had to abide by that, while at the same time he was convinced that it would be very damaging to Britain if he said anything to the parliamentary committee to show the close involvement of Sir Hercules Robinson and Joseph Chamberlain in their disreputable encouragement of those plotting an uprising in Johannesburg.' Finally, Cousins observes that, '...in his reflections, Bower has a particularly damning judgement on Chamberlain, whom he accuses of ‘brazen lying’ to parliament, and of what amounted to forgery in the documents made public for the inquiry. In the report of the committee, Bower was found culpable of complicity, while no blame was attached to Chamberlain or Robinson. His name was never cleared during his lifetime, and Bower was never reinstated to what he believed should be his proper position in the colonial service: he was, in effect, demoted to the post of colonial secretary in Mauritius. The bitterness and sense of betrayal he felt come through very clearly in his comments.' Speculation on the true nature of the behind-the-scenes story of the Jameson Raid has therefore continued for more than a hundred years after the events, and carries on to this day.