Casement was born near Dublin, living in very early childhood at Doyle's Cottage, Lawson Terrace, Sandycove. His Protestant father, Captain Roger Casement of (The King’s Own) Regiment of Light Dragoons, was the son of a bankrupt Belfast shipping merchant (Hugh Casement) who later moved to Australia. Captain Casement served in the 1842 Afghan campaign. Casement's mother Anne Jephson of Dublin had him rebaptised secretly as a Roman Catholic when he was three in Rhyl .She died in Worthing when her son was nine. According to an 1892 letter, Casement believed that she was descended from the Jephson family of Mallow, County Cork. However the Jephson family's historian provides no evidence of this. By the time he was thirteen, his father was also dead, having ended his days in Ballymena dependent on the charity of relatives. Roger was afterwards raised by Protestant paternal relatives in Ulster, the Youngs of Galgorm Castle in Ballymena and the Casements of Magherintemple, and was educated at the Diocesan School, Ballymena, later Ballymena Academy. He left school at 16 and took up a clerical job with Elder Dempster, a Liverpool shipping company headed by Alfred Lewis Jones, later an enemy on the Congo issue.

In 1903, Roger Casement, then the British Consul at Boma, was commissioned by the British government to investigate the human rights situation in the Congo Free State. A long, detailed eyewitness report exposing abuses, the Casement Report, was delivered in 1904. The Congo Free State had been in the possession of King Leopold II of Belgium since 1885, when it was granted to him by the Berlin Conference. Leopold had exploited the territory's natural resources (mostly rubber) as a private entrepreneur, not as King of the Belgians. Casement's report would be instrumental in Leopold finally relinquishing his personal holdings in Africa. When the report was made public, the Congo Reform Association, founded by E.D. Morel, with Casement's support, demanded action. Other European nations followed suit, as did the United States, and the British Parliament demanded a meeting of the 14 signatory powers to review the 1885 Berlin Agreement. The Belgian Parliament, pushed by socialist leader Emile Vandervelde and other critics of the king's Congolese policy, forced Léopold to set up an independent commission of inquiry, and in 1905, despite his efforts, it confirmed the essentials of Casement's report. On 15 November, 1908, the parliament of Belgium took over the Congo Free State from Leopold and organised its administration as the Belgian Congo.

In 1906, Casement was sent to Brazil, first as consul in Pará, then transferred to Santos, and lastly promoted to consul-general in Rio de Janeiro. When he was attached as a consular representative to a commission investigating murderous rubber slavery by the British-registered Peruvian Amazon Company, effectively controlled by the archetypal rubber baron Julio César Arana and his brother, Casement had the occasion to do work among the Putumayo Indians of Peru similar to that which he had done in the Congo. Public outrage in Britain over the abuses against the Putumayo had been sparked in 1909 by articles in the British magazine Truth. Casement paid two visits to the region, first in 1910 and then a follow-up in 1911. In a report to the British foreign secretary, dated 17 March, 1911, Casement detailed the rubber company's use of stocks to punish the Indians:

Men, women, and children were confined in them for days, weeks, and often months. ... Whole families ... were imprisoned -- fathers, mothers, and children, and many cases were reported of parents dying thus, either from starvation or from wounds caused by flogging, while their offspring were attached alongside of them to watch in misery themselves the dying agonies of their parents.

After his return to Britain, he repeated his extra-consular campaigning work by organising Anti-Slavery Society and mission interventions in the region, which was disputed between Peru and Colombia. Some of the men exposed as killers in his report were charged by Peru, while others fled. Conditions in the area undoubtedly improved as a result, but the contemporary switch to farmed rubber in other parts of the world was a godsend to the Indians as well. Arana himself was never prosecuted. He instead went on to have a successful political career, becoming a senator and dying in Lima, Peru, in 1952 at age eighty-eight.

Casement wrote extensively (as always) in those two years including several of his notorious diaries, the one for 1911 being unusually discursive. They and the 1903 diary were kept by him in London with other papers of the period, presumably so they could be consulted in his continuing work as 'Congo Casement' and the saviour of the Putumayo Indians. In 1911, Casement was knighted by George V as Knight Bachelor for his efforts on behalf of the Amazonian Indians, having been reluctantly appointed Companion of the Order of St Michael and St George (CMG) in 1905 for his Congo work.

Casement retired from the consular service in the summer of 1913. In November that year, he helped form the Irish Volunteers with Eoin MacNeill, later the organisation's chief of staff. They co-wrote the Volunteers' manifesto. In July 1914, Casement journeyed to the U.S. to promote and raise money for the Volunteers. Through his friendship with men such as Bulmer Hobson, who was a member of the Volunteers and the Irish Republican Brotherhood (IRB), Casement established connections with exiled Irish nationalists, particularly in Clan na Gael. Elements of the Clan did not trust him completely, as he was not a member of the IRB and held views considered by many to be too moderate, although others such as John Quinn regarded him as extreme. John Devoy, who was initially hostile to Casement for his part in conceding control of the Irish Volunteers to Redmond, in June was won over, while the more extreme Clan leader Joseph McGarrity became and remained devoted to Casement. The Howth gun-running in late July 1914 which he had helped to organise and finance further enhanced Casement's reputation.

In September 1914, after the First World War had broken out, Casement attempted to secure German aid for Irish independence in New York negotiations with the German Ambassador to the US, eventually sailing for Germany via Norway in October. He viewed himself as an ambassador of the Irish nation. While the journey was his idea, Clan na Gael financed the expedition. In Christiania (Oslo), his companion Adler Christensen was taken to the British legation and, according to him, offered a reward if Casement was "knocked on the head." The British minister, in contrast, advised London that Christensen had approached them, and also said that he “implied that their relations were of an unnatural nature and that consequently he had great power over this man.” It was this episode that first provided London with the intimation that Casement was homosexual.

In November 1914, Casement negotiated a declaration by Germany which stated, "The Imperial Government formally declares that under no circumstances would Germany invade Ireland with a view to its conquest or the overthrow of any native institutions in that country. Should the fortune of this great war, that was not of Germany’s seeking ever bring in its course German troops to the shores of Ireland, they would land there not as an army of invaders to pillage and destroy but as the forces of a Government that is inspired by goodwill towards a country and people for whom Germany desires only national prosperity and national freedom”. He negotiated in Berlin with Arthur Zimmermann, then Under Secretary of State in the Foreign Office, and with the Imperial Chancellor, Theobald von Bethmann Hollweg.

Most of his time in Germany, however, was spent in an attempt to recruit an "Irish Brigade" consisting of Irish prisoners-of-war in the prison camp of Limburg an der Lahn, who would be trained to fight against Britain. During the war, Casement is also known to have been involved in the Hindu–German Conspiracy, recommending Joseph McGarrity to Franz von Papen as an intermediary for the plot. The Indian nationalists may also have followed Casement's strategy in attempting to recruit from amongst Indian prisoners of war.

However, both efforts proved unsuccessful. The Irish plan failed, as all Irishmen fighting in the British army did so voluntarily, while recruits to Casement's brigade were liable to the death penalty if Britain won. It was largely abandoned after much time and money were wasted. The Germans, who were sceptical of Casement, but nonetheless aware of the military advantage they could gain from an uprising in Ireland, only in April 1916 offered the Irish 20,000 rifles, 10 machine guns and accompanying ammunition, a fraction of the quantity of weaponry Casement had hoped for, and no German officers.

Casement did not learn about the Easter Rising until after the plan was fully developed. The IRB purposely kept him in the dark and even tried to replace him. Casement may never have learned that it was not the Volunteers who were planning the rising, but IRB members such as Patrick Pearse and Tom Clarke who were pulling the strings behind the scenes.

The German weapons were never landed in Ireland. The ship transporting them, a German cargo vessel called the Libau, was intercepted, even though it had been thoroughly disguised as a Norwegian vessel, Aud Norge. All the crew were German sailors, but their clothes and effects, even the charts and books on the bridge, were Norwegian. The British, however, had intercepted German communications out of Washington and knew there was going to be an attempt to land arms, even if the Royal Navy was not precisely aware of where. The arms ship under Captain Karl Spindler was eventually apprehended by HMS Bluebell on the late afternoon of Good Friday. About to be escorted into Queenstown (now Cobh, Co. Cork) on the morning of Saturday, 22 April, after surrendering, the Aud Norge was scuttled by pre-set explosive charges. Her crew became prisoners of war.

Casement confided his personal papers to Dr. Charles Curry, with whom he had stayed at Riederau on the Ammersee, before he left Germany. He departed with Robert Monteith in a submarine, initially the U-20, which developed engine trouble, and then the U-19, shortly after the Aud sailed. According to Monteith, Casement believed that the Germans were toying with him from the start and providing inadequate aid that would doom a rising to failure, and that he had to reach Ireland before the shipment of arms and convince Eoin MacNeill (who he believed was still in control) to cancel the rising. Indeed, Casement sent a recently arrived Irish-American, John McGoey, through Denmark to Dublin, ostensibly to advise of what military aid was coming from Germany and when, but with Casement's orders "to get the Heads in Ireland to call off the rising and merely try to land the arms and distribute them". McGoey however did not make it to Dublin, nor did his message. His fate is unknown. Despite any view ascribed to Monteith, Casement expected to be involved in the rising if it went ahead.

In the early hours of 21 April 1916, three days before the rising began, Casement was put ashore at Banna Strand in Tralee Bay, County Kerry. Too weak to travel, he was discovered at McKenna's Fort (an ancient ring fort now called Casement's Fort) in Rathoneen, Ardfert, and subsequently arrested on charges of treason, sabotage, and espionage against the Crown. He was taken straight to the Tower of London where he was imprisoned, but not before he was able to send word to Dublin about the inadequate German assistance.

Despite a highly publicised trial, the government, to their embarrassment, found little legal basis on which to prosecute Casement because his crimes had been carried out in Germany and the Treason Act seemed to apply only to activities carried out on British soil. However, closer reading of the medieval document allowed for a broader interpretation, leading to the accusation that Casement was "hanged by a comma". The court decided that a comma should be read in the text, crucially widening the sense so that "in the realm or elsewhere" meant where acts were done and not just where the "King's enemies" may be. After an unsuccessful appeal against the conviction and death sentence, he was hanged at Pentonville Prison in London on 3 August 1916, at the age of 51. He underwent the Rite of Christian Initiation of Adults into the Catholic Church while awaiting execution and went to his death, he said, with the body of his God as his last meal.

Among the many people who pleaded for clemency were Sir Arthur Conan Doyle, who became acquainted with Casement through the work of the Congo Reform Association, W. B. Yeats and George Bernard Shaw. Edmund Dene Morel could not visit him in jail, being under attack for his pacifist position. On the other hand, Joseph Conrad, who had a son at the front, could not forgive Casement for his treachery toward Britain nor did his friend the sculptor Herbert Ward. Members of the Casement family in Antrim contributed discreetly to the defence fund, although they had sons in the army and navy.

Before his execution, photographs of so-called "Black Diaries" which the government claimed belonged to Casement were circulated to those urging commutation of his death sentence. The documents, which covered the years 1903, 1910 and 1911, showed Casement to have been a promiscuous homosexual with a fondness for young men. In a time of strong social conservatism, not least among Irish Catholics, the Black Diaries undermined or at least stifled support for Casement. Archbishop Davidson, concerned at the rumours, arranged for John Harris of the Anti-Slavery Society, and a missionary friend of Casement's, to view the diaries; Harris was shattered when he realised they were authentic. The statement found in a number of books (usually without source) that Archbishop Davidson consequently abandoned his attempts to seek clemency is incorrect. The Archbishop made his plea for Casement's life to the Lord Chancellor, Lord Buckmaster, on 1 August, two days before the execution. Though some believed that the diaries were forgeries, much as Charles Stewart Parnell had been the target of the Pigott forgeries implicating him in the Phoenix Park Murders, others did not. H. Montgomery Hyde, an Ulster Unionist Party MP and barrister who campaigned for the release of the Black Diaries in Parliament in the 1950s and who wrote a book on Casement's trial, had no doubt that Casement had been a pederast. In 2002, an independent forensic examination of the diaries, commissioned by a team of academics from Goldsmiths, University of London and funded by RTÉ and the BBC, was undertaken by Dr. Audrey Giles, an internationally respected figure in the field of document forensics. Giles compared Casement's White Diaries (ordinary diaries of the time) with the Black Diaries and concluded that the Black Diaries were genuine. American document examiner and expert James Horan later rejected Giles's conclusion on the grounds that the "control" material (the "authentic" handwriting of Casement) taken from the Morel archive at LSE, may have passed through the hands of British Intelligence after Morel's arrest in 1917. Horan's view was that the conclusion would not stand up in a US court. However such a test was not a requirement in the Giles report remit for judging authenticity, and Horan accepted he had not seen any of the material in question.

Roger Sawyer’s 1997 work on the 1910 diary and Jeffrey Dudgeon’s massive and closely footnoted edition of all the Black Diaries in 2002, accompanied by a perceptive and empathetic biographical treatment, went a long way towards integrating Casement’s nationalist, humanitarian and homosexual lives, and Casement's most recent biographer, Séamas Ó Síocháin, accepts their authenticity as a matter of course. The diaries may now be inspected at the British National Archives in Kew.

As was the custom at the time, Casement's body was buried in quicklimein the prison cemetery at the rear of Pentonville Prison, where he was hanged. In 1965, Casement's body was repatriated to Ireland and, after a state funeral, was buried with full military honours in the Republican plot in Glasnevin Cemetery in Dublin after lying in state at Arbour Hill for five days, during which time over half a million people are estimated to have filed past his coffin. The President of Ireland, Éamon de Valera, who in his mid-eighties was the last surviving leader of the Easter Rising, defied the advice of his doctors and attended the ceremony, along with an estimated 30,000 Irish citizens. Casement's last wish, to be buried at Murlough Bay on the North Antrim coast has yet to be fulfilled as Harold Wilson's government only released the remains on condition that they not be brought into Northern Ireland.