Arthur Conan Doyle was born as the third of ten siblings on 22 May 1859 in Edinburgh, Scotland. His father, Charles Altamont Doyle, was born in England of Irish descent, and his mother, born Mary Foley, was Irish. They were married in 1855. Although he is now referred to as "Conan Doyle", the origin of this compound surname (if that is how he meant it to be understood) is uncertain. The entry in which his baptism is recorded in the register of St Mary's Cathedral in Edinburgh gives 'Arthur Ignatius Conan' as his Christian name, and simply 'Doyle' as his surname. It also names Michael Conan as his godfather. Conan Doyle was sent to the Roman Catholic Jesuit preparatory school Hodder Place, Stonyhurst, at the age of nine. He then went on to Stonyhurst College until 1875.

From 1876 to 1881 he studied medicine at the University of Edinburgh, including a period working in the town of Aston (now a district of Birmingham) and in Sheffield. While studying, Conan Doyle also began writing short stories; his first published story appeared in Chambers's Edinburgh Journal before he was 20. Following his term at university, he was employed as a ship's doctor on the SS Mayumba during a voyage to the West African coast. He completed his doctorate on the subject of tabes dorsalis in 1885.

In 1882 he joined former classmate George Budd as his partner at a medical practice in Plymouth, but their relationship proved difficult, and Conan Doyle soon left to set up an independent practice. Arriving in Portsmouth in June of that year with less than £10 to his name, he set up a medical practice at 1 Bush Villas in Elm Grove, Southsea. The practice was initially not very successful; while waiting for patients, Conan Doyle again began writing stories. His first significant work, A Study in Scarlet, appeared in Beeton's Christmas Annual for 1887. It featured the first appearance of Sherlock Holmes, who was partially modelled after his former university professor Joseph Bell. Conan Doyle wrote to him, "It is most certainly to you that I owe Sherlock Holmes. ... [R]ound the centre of deduction and inference and observation which I have heard you inculcate I have tried to build up a man." Future short stories featuring Sherlock Holmes were published in the English Strand Magazine. Interestingly enough, Robert Louis Stevenson was able, even in faraway Samoa, to recognise the strong similarity between Joseph Bell and Sherlock Holmes: "[M]y compliments on your very ingenious and very interesting adventures of Sherlock Holmes. ... [C]an this be my old friend Joe Bell?" Other authors sometimes suggest additional influences — for instance, the famous Edgar Allan Poe character C. Auguste Dupin.

While living in Southsea, he played football as a goalkeeper for an amateur side, Portsmouth Association Football Club, under the pseudonym A.C. Smith. (This club, disbanded in 1894, had no connection with the present day Portsmouth F.C., which was founded in 1898.) Conan Doyle was also a keen cricketer, and between 1899 and 1907 he played 10 first-class matches for the Marylebone Cricket Club (MCC). His highest score, in 1902 against London County, was 43. He was an occasional bowler who took just one first class wicket (although one of high pedigree — it was W.G. Grace). Also a keen golfer, Conan Doyle was elected captain of the Crowborough Beacon Golf Club, East Sussex, for 1910. He moved to Little Windlesham house in Crowborough with his second wife Jean Leckie and their family from 1907 until his death in July 1930.

In 1885 Conan Doyle married Louisa (or Louise) Hawkins, known as "Touie". She suffered from tuberculosis and died on 4 July 1906. The next year he married Jean Elizabeth Leckie, whom he had first met and fallen in love with in 1897. He had maintained a platonic relationshipwith Jean while his Louisa was still alive, out of loyalty to her. Jean died in London on 27 June 1940. Conan Doyle fathered five children. He had two with his first wife — Mary Louise (28 January 1889 – 12 June 1976) and Arthur Alleyne Kingsley, known as Kingsley (15 November 1892 – 28 October 1918) — and three with his second wife — Denis Percy Stewart (17 March 1909 – 9 March 1955), second husband in 1936 of Georgian Princess Nina Mdivani (circa 1910 – 19 February 1987; former sister-in-law of Barbara Hutton); Adrian Malcolm (19 November 1910 – 3 June 1970) and Jean Lena Annette (21 December 1912 – 18 November 1997).

In 1890 Conan Doyle studied the eye in Vienna, and moved to London in 1891 to set up a practice as an ophthalmologist. He wrote in his autobiography that not a single patient crossed his door. This gave him more time for writing, and in November 1891 he wrote to his mother: "I think of slaying Holmes ... and winding him up for good and all. He takes my mind from better things." His mother responded, "You may do what you deem fit, but the crowds will not take this lightheartedly."

In December 1893, in order to dedicate more of his time to more "important" works — his historical novels — Conan Doyle had Holmes and Professor Moriarty apparently plunge to their deaths together down the Reichenbach Falls in the story "The Final Problem". Public outcry, however, led him to bring the character back in 1901, in The Hound of the Baskervilles. In "The Adventure of the Empty House", it was explained that only Moriarty had fallen; but since Holmes had other dangerous enemies — especially Colonel Sebastian Moran — he had arranged to also be temporarily "dead". Holmes ultimately was featured in a total of 56 short stories and four Conan Doyle novels, and has since appeared in many novels and stories by other authors.

Following the Boer War in South Africa at the turn of the 20th century and the condemnation from around the world over the United Kingdom's conduct, Conan Doyle wrote a short pamphlet titled The War in South Africa: Its Cause and Conduct, which justified the UK's role in the Boer War and was widely translated. Doyle had served as a volunteer doctor in the Langman Field Hospital at Bloemfontein between March and June 1900. Conan Doyle believed it was this pamphlet that resulted in his being knighted in 1902 and appointed Deputy - Lieutenant of Surrey. Also in 1900 he wrote the longer book, The Great Boer War. During the early years of the 20th century, Sir Arthur twice ran for Parliament as a Liberal Unionist — once in Edinburgh and once in the Hawick Burghs — but although he received a respectable vote, he was not elected.

Conan Doyle was involved in the campaign for the reform of the Congo Free State, led by journalist E.D. Morel and diplomat Roger Casement. During 1909 he wrote The Crime of the Congo, a long pamphlet in which he denounced the horrors in that country. He became acquainted with Morel and Casement, and it is possible that, together with Bertram Fletcher Robinson, they inspired several characters in the 1912 novel The Lost World. He broke with both when Morel became one of the leaders of the pacifist movement during the First World War, and when Casement was convicted of treason against the UK during the Easter Rising. Conan Doyle tried unsuccessfully to save Casement from the death penalty, arguing that he had been driven mad and was not responsible for his actions.

Conan Doyle was also a fervent advocate of justice and personally investigated two closed cases, which led to two men being exonerated of the crimes of which they were accused. The first case, in 1906, involved a shy half-British, half-Indian lawyer named George Edalji who had allegedly penned threatening letters and mutilated animals. Police were set on Edalji's conviction, even though the mutilations continued after their suspect was jailed. It was partially as a result of this case that the Court of Criminal Appeal was established in 1907, so not only did Conan Doyle help George Edalji, his work helped establish a way to correct other miscarriages of justice. The story of Conan Doyle and Edalji was fictionalized in Julian Barnes's 2005 novel Arthur & George. In Nicholas Meyer's pastiche "The West End Horror" (1976), Holmes manages to help clear the name of a shy Parsee Indian character wronged by the English justice system. Edalji himself was a Parsee. The second case, that of Oscar Slater, a German Jew and gambling den operator convicted of bludgeoning an 82-year-old woman in Glasgow in 1908, excited Conan Doyle's curiosity because of inconsistencies in the prosecution case and a general sense that Slater was not guilty. He ended up paying most of the costs for Slater's successful appeal in 1928.

Following the death of his wife Louisa in 1906, the death of his son Kingsley just before the end of World War I, and the deaths of his brother Innes, his two brothers-in-law (one of whom was E.W. Hornung, creator of the literary character Raffles) and his two nephews shortly after the war, Conan Doyle sank into depression. He found solace supporting spiritualism and its attempts to find proof of existence beyond the grave. In particular, according to some, he favoured Christian Spiritualism and encouraged the Spiritualists' National Union to accept an eighth precept - that of following the teachings and example of Jesus of Nazareth. He also was a member of the renowned paranormal organisation The Ghost Club. Its focus, then and now, is on the scientific study of alleged paranormal activities in order to prove (or refute) the existence of paranormal phenomena.

On 28 October 1918 Kingsley Doyle died from pneumonia, which he contracted during his convalescence after being seriously wounded during the 1916 Battle of the Somme. Brigadier General Innes Doyle died, also from pneumonia, in February 1919. Sir Arthur became involved with Spiritualism to the extent that he wrote a Professor Challenger novel on the subject, The Land of Mist.

His book The Coming of the Fairies (1921) shows he was apparently convinced of the veracity of the five Cottingley Fairies photographs (which decades later were exposed as a hoax). He reproduced them in the book, together with theories about the nature and existence of fairies and spirits. In The History of Spiritualism (1926), Conan Doyle praised the psychic phenomena and spirit materialisations produced by Eusapia Palladino and Mina "Margery" Crandon. His work on this topic was one of the reasons that one of his short story collections, The Adventures of Sherlock Holmes, was banned in the Soviet Union in 1929 for supposed occultism. This ban was later lifted. Russian actor Vasily Livanov later received an Order of the British Empire for his portrayal of Sherlock Holmes.

Conan Doyle was friends for a time with Harry Houdini, the American magician who himself became a prominent opponent of the Spiritualist movement in the 1920s following the death of his beloved mother. Although Houdini insisted that Spiritualist mediums employed trickery (and consistently exposed them as frauds), Conan Doyle became convinced that Houdini himself possessed supernatural powers — a view expressed in Conan Doyle's The Edge of the Unknown. Houdini was apparently unable to convince Conan Doyle that his feats were simply illusions, leading to a bitter public falling out between the two.

Richard Milner, an American historian of science, has presented a case that Conan Doyle may have been the perpetrator of the Piltdown Man hoax of 1912, creating the counterfeit hominid fossil that fooled the scientific world for over 40 years. Milner says that Conan Doyle had a motive — namely, revenge on the scientific establishment for debunking one of his favourite psychics — and that The Lost World contains several encrypted clues regarding his involvement in the hoax.

Samuel Rosenberg's 1974 book Naked is the Best Disguise purports to explain how, throughout his writings, Conan Doyle left open clues that related to hidden and suppressed aspects of his mentality.

Conan Doyle was found clutching his chest in the hall of Windlesham, his house in Crowborough, East Sussex, on 7 July 1930. He died of a heart attack at age 71. His last words were directed toward his wife: "You are wonderful." The epitaph on his gravestone in the churchyard at Minstead in the New Forest, Hampshire, reads:

STEEL TRUE
BLADE STRAIGHT
ARTHUR CONAN DOYLE
KNIGHT
PATRIOT, PHYSICIAN & MAN OF LETTERS

Undershaw, the home near Hindhead, south of London that Conan Doyle had built and lived in for at least a decade, was a hotel and restaurant from 1924 until 2004. It was then bought by a developer, and has since been empty while conservationists and Conan Doyle fans fight to preserve it.

A statue honours Conan Doyle at Crowborough Cross in Crowborough, where Conan Doyle lived for 23 years. There is also a statue of Sherlock Holmes in Picardy Place, Edinburgh, close to the house where Conan Doyle was born.