Treves became a surgeon, specialising in abdominal surgery, at the London Hospital in the late nineteenth and early twentieth century. He performed the first appendectomy in England, on 29 June 1888.
In 1884, Treves first saw Joseph Merrick, known as the Elephant Man, being exhibited by showman Tom Norman in a shop across the road from the London Hospital. Around 1886 Treves brought Merrick to the London Hospital where Merrick lived until his death in April 1890. Treves' reminiscences mistakenly names Joseph Merrick as John Merrick, an error widely recirculated by biographers of Merrick.
During the Second Boer War (1899–1902), Treves volunteered to work at a field hospital in South Africa treating the wounded. He later published an account of his experiences in The Tale of a Field Hospital, based on articles written at the time for the British Medical Journal.
In late March 1901, Treves was appointed one of several Honorary Serjeants Surgeon to King Edward VII, and in May the same year was knighted as a Knight Commander of the Royal Victorian Order (KCVO). The coronation of the new king was scheduled for 26 June, but on 24 June, Edward was diagnosed with appendicitis. Treves, with the support of the leading surgical authority, Lord Lister, performed a then-radical operation of draining the infected appendix through a small incision. This was at a time when appendicitis was generally not treated operatively and carried a high mortality rate.The King had opposed surgery for this reason but Treves insisted, stating that if he was not permitted to operate, there would instead be a funeral. The next day, Edward was sitting up in bed, smoking a cigar.
Treves was honoured with a baronetcy (which Edward had arranged before the operation) and appendix surgery entered the medical mainstream in the UK. He was granted the use of Thatched House Lodge in Richmond Park and was subsequently able to take early retirement, but continued as Serjeant Surgeon to the King and to the Royal Household until 1910.