Brett was born in Berkswell Grange, Warwickshire, England. He was educated at Eton College. Brett later claimed that he was an "academic disaster" at Eton and attributed his learning difficulties to dyslexia. However, he excelled at singing and was a member of the choir while at Eton.

Jeremy Brett trained as an actor at the Central School of Speech and Drama in London. He made his professional acting debut at the Library Theatre in Manchester in 1954. Brett made his London stage debut with the Old Vic company in 1956. He would go on to play many classical roles on stage, including numerous Shakespearean parts in his early career with the Old Vic and later with the Royal National Theatre. Brett made his first television appearance in 1954 and his first feature film appearance in 1955.

In 1958, Jeremy Brett married the actress, Anna Massey (daughter of Raymond Massey), but they divorced in 1962 (they had a son named David Huggins, born 1959, who is now a successful British novelist). Years later, Brett and Massey appeared together in the BBC's dramatization of Rebecca (1978), with Brett playing the haunted hero, Max de Winter, and Massey playing the sinister housekeeper, Mrs. Danvers. (David Huggins also played a bit part in the film.)

In 1976 Brett married American PBS producer Joan Wilson, but she died of cancer in 1985. Brett was devastated by Wilson's untimely death and he never remarried.

From the early 1960s onwards, Brett was rarely absent from British television screens. He starred in many classic serials, notably appearing as D'Artagnan in the 1966 adaptation of The Three Musketeers. A few of his appearances were in comedic roles, but usually with a classic edge, such as Captain Absolute in The Rivals. In 1973, Brett portrayed Bassanio in a televised production of William Shakespeare's The Merchant of Venice, in which Laurence Olivier portrayed Shylock and Joan Plowright portrayed Portia. (Brett, Olivier and Plowright had previously played the same roles in a Royal National Theatre production of the play.) Brett joked that, as an actor, he was rarely allowed into the 20th century and never into the present day.

Although Brett's feature film appearances were relatively few and far between, he did play Freddie Eynsford-Hill in the 1964 blockbuster film version of My Fair Lady. His singing voice was dubbed in the film, but Old Etonian Brett could still sing, as he later proved when he played Danilo in The Merry Widow on British television in 1968.

Notable in all of Jeremy Brett's roles is his precisely honed diction. Brett was born with a speech impediment that kept him from pronouncing the "R" sound correctly. Corrective surgery as a teenager, followed by years of practising to pronounce sounds correctly, gave Brett an enviable, flawless pronunciation and enunciation. He later claimed he practised all of his speech exercises daily, whether he was working or not, to keep his diction fit.

Although he appeared in many films and television series during his 40-year career, Jeremy Brett is now best remembered for portraying Sherlock Holmes in a decade-long (1984 to 1994) series of Granada Television films, adapted by John Hawkesworth and other writers from the original Holmes stories by Sir Arthur Conan Doyle (see The Adventures of Sherlock Holmes (television)). After taking on the demanding role, Brett made few other acting appearances but he is now widely considered to be the definitive Holmes of his era, just as Basil Rathbone was during the 1940s - although Brett's fans consider his performance to be the best of all the many portrayals of the famous detective.

Brett suffered from bipolar disorder (commonly known as manic depression), which worsened after Joan Wilson's death. Joan died shortly after Brett finished filming Holmes’ “death” in “The Final Problem.” He took a break from filming the series, but when he returned to filming in 1986 he suffered a nervous breakdown caused by his bipolar disorder aggravated by grief and the stressful shooting schedule. During the last decade of his life, Brett was hospitalized several times for treatment of his mental illness, and his health and appearance had visibly deteriorated by the time he made the later episodes of the Holmes TV series.

Although he reportedly feared being typecast, Brett appeared in forty-two episodes of the Granada series. There were plans to film all the Holmes stories, but Brett died of heart failure at his home in London before the project could be completed. Brett's heart had been damaged by a childhood case of rheumatic fever, and was apparently further weakened by the various drugs prescribed to control his manic depressive episodes, particularly Lithium salt, and by his heavy cigarette smoking. He died at the age of 61 on September 12, 1995.

Jeremy Brett is related to another noted British actor, Martin Clunes (of Men Behaving Badly fame) - Clunes' mother was Brett's first cousin.