Brodie was born in Winterslow, Wiltshire. He received his early education from his father; then choosing medicine as his profession he went to London in 1801 and attended the lectures of John Abernethy. Two years later he became a pupil of Sir Everard Home at St George's Hospital, and in 1808 was appointed assistant surgeon at that institution, on the staff of which he served for over thirty years. In 1820 he was elected a fellow of the Royal Society, to which in the next four or five years he contributed several papers describing original investigations in physiology.
At this period he also rapidly obtained a large and lucrative practice and from time to time wrote on surgical questions, contributing numerous papers to the Medical and Chirurgical Society and to the medical journals. His most important work is widely acknowledged to be the 1818 treatise Pathological and Surgical Observations on the Diseases of the Joints, in which he attempts to trace the beginnings of disease in the different tissues that form a joint and to give an exact value to the symptom of pain as evidence of organic disease. This volume led to the adoption by surgeons of more conservative measures in the treatment of diseases of the joints, with consequent reduction in the number of amputations and the saving of many limbs and lives. He also wrote on diseases of the urinary organs and on local nervous affections of a surgical character.
In 1854 he published anonymously a volume of Psychological Inquiries—eight years later, the expanded, revised and updated 1862 volume appeared under his name. He received many honours during his career and attended to the health of the Royal Family, starting with George IV. He was also sergeant-surgeon to William IV and Queen Victoria and was made a baronet in 1834. He became a corresponding member of the French Institute in 1844, DCL of Oxford in 1855, president of the Royal Society in 1858 and subsequently, the first president of the General Medical Council.
Sir Benjamin Collins Brodie died in Broome Park, Surrey at the age of 79. His collected works, with autobiography, were published in 1865 under the editorship of Charles Hawkins.
Brodie's eldest son, Sir Benjamin Collins Brodie, 2nd Baronet, was appointed professor of chemistry at Oxford in 1865, and is chiefly known for his investigations on the allotropic states of carbon and for his discovery of graphitic acid.