Born Mary Patricia Plangman in Fort Worth, Texas. She lived in her maternal grandmother's boarding house with her mother, and later her stepfather. In 1927 she moved to New York City with her mother and stepfather. When Highsmith was 12 years old, she was taken to Fort Worth and lived with her grandmother for a year. She called this the "saddest year" of her life, and felt abandoned by her mother. She returned to New York to continue living with her mother and stepfather, Stanley Highsmith. Highsmith's mother Mary had divorced "Patsy's" father (Jay Bernard Plangman) five months before her birth, and he is absent from the family's history after that. The young Highsmith had an intense, complicated relationship with her mother and resented her stepfather, although she took his surname, and in later years she sometimes tried to win him over to her side of the argument in her confrontations with her mother. According to Highsmith, her mother once told her that she had tried to abort her by drinking turpentine. Highsmith never resolved this love-hate relationship, which haunted her for the rest of her life, and which she fictionalized in her short story "The Terrapin", about a young boy who stabs his mother to death.

Highsmith's grandmother taught her to read at an early age. Highsmith made good use of her grandmother's extensive library. At the age of eight, she discovered Karl Menninger's The Human Mind and was fascinated by the case studies of patients afflicted with mental disorders such as pyromania and schizophrenia.

In 1942 Highsmith graduated from Barnard College, where she had studied English composition, playwriting and the short story. Living in New York City and Mexico between 1942 and 1948, she wrote for comic book publishers. Answering an ad for "reporter/rewrite," she arrived at the office of comic book publisher Ned Pines and landed a job working in a bullpen with four artists and three other writers. Initially scripting two comic book stories a day for $55-a-week paychecks, she soon realized she could make more money by writing freelance for comics, a situation which enabled her to find time to work on her own short stories and also live for a period in Mexico. The comic book scriptwriter job was the only long-term job she ever held.

With Nedor/Standard/Pines (1942—43), she wrote Sgt. Bill King stories and contributed to Black Terror. For Real Fact, Real Heroes and True Comics, she wrote comic book profiles of Einstein, Galileo, Barney Ross, Edward Rickenbacker, Oliver Cromwell, Sir Isaac Newton, David Livingstone and others. In 1943—45 she wrote for Fawcett Publications, scripting for such Fawcett Comics characters as the Golden Arrow, Spy Smasher, Captain Midnight, Crisco and Jasper. She wrote for Western Comics in 1945—47.

When she wrote The Talented Mr. Ripley (1955), one of the title character's first scam victims is comic-book artist Frederick Reddington, a parting gesture directed at the earlier career she had abandoned: "Tom had a hunch about Reddington. He was a comic-book artist. He probably didn't know whether he was coming or going."

Highsmith's first novel was Strangers on a Train, which emerged in 1950, and which contained the violence that became her trademark. At Truman Capote's suggestion, she rewrote the novel at the Yaddo writer's colony in Saratoga Springs, New York. The book proved modestly successful when it was published in 1950. However, Hitchcock's 1951 film adaptation of the novel propelled Highsmith's career and reputation. Soon she became known as a writer of ironic, disturbing psychological mysteries highlighted by stark, startling prose.

Highsmith's second novel, The Price of Salt was published under the pseudonym Claire Morgan. It garnered wide attention as a lesbian novel because of its rare happy ending. She did not publicly associate herself with this book until late in her life, probably because she had extensively mined her personal life for the book's content.

As her other novels were issued, moviemakers adapted them for screenplays: The Talented Mr. Ripley (1955), Ripley's Game (1974) and Edith's Diary (1977) all became films.

She was a lifelong diarist, and developed her writing style as a child writing entries in which she fantasized that her neighbours had psychological problems and murderous personalities behind their façades of normality, a theme she would explore extensively in her novels.

Highsmith included homosexual undertones in many of her novels and addressed the theme directly in The Price of Salt and the posthumously published Small g: a Summer Idyll. The former novel is known for its happy ending, the first of its kind in lesbian fiction. Published in 1952 under the pseudonym Claire Morgan, it sold almost a million copies. The inspiration for the book's main character, Carol, was a woman Highsmith saw in Bloomingdale's department store, where she worked at the time. Highsmith found out her address from the credit card details, and on two occasions after the book was written (in June 1950 and January 1951) spied on the woman without the latter's knowledge.

The protagonists in many of Highsmith's novels are either morally compromised by circumstance or actively flouting the law. Many of her antiheroes, often emotionally unstable young men, commit murder in fits of passion, or simply to extricate themselves from a bad situation. They are just as likely to escape justice as to receive it. The works of Franz Kafka and Fyodor Dostoevsky played a significant part in her own novels.

Her recurring character Tom Ripley ... an amoral, sexually ambiguous con artist and occasional murderer ... was featured in a total of five novels, popularly known as the Ripliad, written between 1955 and 1991. He was introduced in The Talented Mr. Ripley. After a 9 January 1956 TV adaptation on Studio One, it was filmed by René Clément as Plein Soleil (1960, aka Purple Noon and Blazing Sun) with Alain Delon, whom Highsmith praised as the ideal Ripley. The novel was adapted under its original title in the 1999 film directed by Anthony Minghella, starring Matt Damon, Gwyneth Paltrow, Jude Law and Cate Blanchett.

A later Ripley novel, Ripley's Game, was filmed by Wim Wenders as The American Friend (1977). Under its original title, it was filmed again in 2002, directed by Liliana Cavani with John Malkovich in the title role. Ripley Under Ground (2005), starring Barry Pepper as Ripley, was shown at the 2005 AFI Film Festival but has not had a general release.

In 2009 BBC Radio 4 adapted all five Ripley books with Ian Hart as Ripley.

According to her biography, Beautiful Shadow, Highsmith's personal life was a troubled one; she was an alcoholic who never had a relationship that lasted for more than a few years, and was seen by some of her contemporaries and acquaintances as misanthropic and cruel. She famously preferred the company of animals to that of people, and once said, "My imagination functions much better when I don't have to speak to people."

"She was a mean, hard, cruel, unlovable, unloving person," said acquaintance Otto Penzler. "I could never penetrate how any human being could be that relentlessly ugly."

Other friends and acquaintances were less caustic in their criticism, however; Gary Fisketjon, who published her later novels through Knopf, said that "she was rough, very difficult... but she was also plainspoken, dryly funny, and great fun to be around."

Though she had occasional relationships with men, Highsmith was a lesbian, and never married or had children. In 1943 she had an affair with the artist Allela Cornell (who subsequently committed suicide in 1946 by drinking nitric acid) and in 1949, she became close to novelist Marc Brandel. Between 1959 and 1961 she had a relationship with Marijane Meaker, who wrote under the pseudonyms of Vin Packer and Ann Aldrich, but later wrote young adult fiction with the name M.E. Kerr. Meaker wrote of their affair in her memoir Highsmith: A Romance of the 1950s.

In the late 1980s, after 27 years of separation, Highsmith began sharing correspondence with Meaker again, and one day showed up on her doorstep, slightly drunk and ranting bitterly. Meaker once recalled in an interview the horror she felt upon noticing the changes in Highsmith's personality by that point.

"Highsmith was never comfortable with blacks, and she was outspokenly anti-semitic ... so much so that when she was living in Switzerland in the 1980s, she invented nearly 40 aliases, identities she used in writing to various government bodies and newspapers, deploring the state of Israel and the 'influence' of the Jews". Nevertheless, some of her best friends were Jewish, such as author Arthur Koestler, and admired Jewish writers such as Franz Kafka and Saul Bellow. She was accused of misogyny because of her satirical collection of short stories Little Tales of Misogyny.

Highsmith loved woodworking tools and made several pieces of furniture. She kept pet snails; she worked without stopping. In her later life she became stooped, with an osteoporotic hump.

Though her writing ... 22 novels and eight books of short stories ... was highly acclaimed, especially outside of the United States, Highsmith preferred for her personal life to remain private. She had friendships and correspondences with several writers, and was also greatly inspired by art and the animal kingdom.

Highsmith believed in American democratic ideals and in the promise of US history, but she was also highly critical of the reality of the country's 20th-century culture and foreign policy. Tales of Natural and Unnatural Catastrophes, her 1987 anthology of short stories, was notoriously anti-American, and she often cast her homeland in a deeply unflattering light. Beginning in 1963, she resided exclusively in Europe. In 1978, she was head of the jury at the 28th Berlin International Film Festival.

Highsmith died of leukemia in Locarno, Switzerland. In gratitude to the place that helped inspire her writing career, she left her estate, worth an estimated $3 million, to the Yaddo colony. Her last novel, Small g: a Summer Idyll, was published posthumously a month later.

Novels

1. Strangers on a Train (1950)
2. The Price of Salt (as Claire Morgan) (1952), also published as Carol
3. The Blunderer (1954)
4. The Talented Mr. Ripley (1955)
5. Deep Water (1957)
6. A Game for the Living (1958)
7. This Sweet Sickness (1960)
8. The Two Faces of January (1961)
9. The Cry of the Owl (1962)
10. The Glass Cell (1964)
11. A Suspension of Mercy (1965), also published as The Story-Teller
12. Those Who Walk Away (1967)
13. The Tremor of Forgery (1969)
14. Ripley Under Ground (1970)
15. A Dog's Ransom (1972)
16. Ripley's Game (1974)
17. Edith's Diary (1977)
18. The Boy Who Followed Ripley (1980)
19. People Who Knock on the Door (1983)
20. Found in the Street (1987)
21. Ripley Under Water (1991)
22. Small g: a Summer Idyll (1995)

Short story collections

1. Eleven (1970; also known as The Snail-Watcher and Other Stories)
2. Little Tales of Misogyny (1974)
3. The Animal Lover's Book of Beastly Murder (1975)
4. Slowly, Slowly in the Wind (1979)
5. The Black House (1981)
6. Mermaids on the Golf Course (1985)
7. Tales of Natural and Unnatural Catastrophes (1987)
8. Nothing That Meets the Eye: The Uncollected Stories (2002; posthumously published)

Collected works

1. The Highsmith Reader (W.W. Norton 2010)

Miscellaneous

1. Plotting and Writing Suspense Fiction (1966)
2. Miranda the Panda Is on the Veranda (1958; children's book of verse and drawings, co-written with Doris Sanders)