Nimoy was born in Boston, Massachusetts to Yiddish-speaking Jewish immigrants from Russia. His mother, Dora Spinner, was a homemaker, and his father, Max Nimoy, was a barbershop operator. After a short enrollment at Boston College, he left formal study to move to California to pursue acting. Nimoy spent much of his early career doing small parts in B-movies, TV shows such as Dragnet, and serials such as Republic Pictures Zombies of the Stratosphere in 1952. He fondly recalls playing in pinochle tournaments and selling his body for medical experiments to pay for tap dance lessons. In 1961 he had a minor role in The Twilight Zone episode "A Quality of Mercy". His Bostonian upbringing can be heard in his pronunciation, for example his pronunciation of the word "rather" in Star Trek episodes.

Nimoy served in the U.S. Army Reserve, receiving final discharge in November 1955 as a Sergeant. According to the National Archives and Records Administration, Nimoy's U.S. Army service record was destroyed in the 1973 National Archives Fire.

Nimoy's most famous role is the half-Vulcan, half-human Spock from Star Trek, The Original Series, which ran from 1966 to 1969. He earned three Emmy nominations for playing this character.

As a foretaste of what was to come, Nimoy and William Shatner (who would go on to play Spock's commanding officer, Captain James T. Kirk) found themselves on the opposite side of the Iron Curtain in the 1964 episode of The Man from U.N.C.L.E., "The Project Strigas Affair". With his saturnine looks, Nimoy was predictably the villain, with Shatner playing a reluctant U.N.C.L.E. recruit. Nimoy went on to reprise Spock's character in a voice-over role in Star Trek: The Animated Series, in two episodes of Star Trek: The Next Generation, and in six Star Trek motion pictures featuring the original cast.

Before his success in Star Trek, Nimoy had acted in more than 50 movies or television shows. Although most of these were popular TV shows, he also appeared in The Balcony, an adaptation of a play by Jean Genet. Following the cancellation of the original Star Trek series, Nimoy immediately joined the cast of the spy series Mission: Impossible, which was seeking a replacement for Martin Landau. Nimoy was cast as an actor-turned-spy known as "The Great Paris". He played the role from 1969 to 1971, on the fourth and fifth seasons of the show. (As noted by Patrick White in The Complete Mission: Impossible Dossier, Landau had been an early choice to play Spock.) It was during the run of the show that Nimoy fell ill with a stomach ulcer.

He co-starred with Yul Brynner and Richard Crenna in the Western movie Catlow (1971). Nimoy also appeared in various made for television films in this period, such as Assault On The Wayne (1970), Baffled (1972), The Alpha Caper (1973), The Missing Are Deadly (1974), Seizure: The Story Of Kathy Morris (1980), Marco Polo (1982) and he received an Emmy award nomination for best supporting actor for the TV film A Woman Called Golda (1982). In 1973, Nimoy also appeared on an episode of the popular television series Columbo called "A Stitch In Crime". He played a murderous doctor and was one of the few criminals at whom Columbo ever really became angry. In the late 1970s, he hosted and narrated the television series In Search of..., which investigated paranormal or unexplained events or subjects. He also has a memorable character part as a mad scientist-type New Age psychologist in Philip Kaufman's remake of Invasion of the Body Snatchers. It was during this time that Nimoy won acclaim for a series of stage roles as well. He has appeared in such plays as Vincent, Fiddler On The Roof, The Man In The Glass Booth, Oliver, Six Rms Riv Vu, Full Circle, Camelot, One Flew Over The Cuckoo's Nest, The King And I, Caligula, The Four Poster, Twelfth Night, Sherlock Holmes, Equus and My Fair Lady. When a new Star Trek series was planned in the late 1970s, Nimoy was to be in only two out of every eleven episodes, but when the show was elevated to a feature film, he agreed to reprise his role.

After directing a few television show episodes, Nimoy broke into film directing in 1984 with the successful third installment of the Star Trek film series (Star Trek III: The Search for Spock). Nimoy would go on to direct Star Trek IV: The Voyage Home (1986) and move beyond the Trek universe with Three Men and a Baby in 1987. Nimoy also did occasional work as a voice actor in animated feature films including the character of Galvatron in Transformers: The Movie in 1986 and The Pagemaster in 1994.

Nimoy has written two autobiographies, the first one called I Am Not Spock (1977). The title of this book was controversial, as many fans incorrectly assumed that Nimoy was distancing himself from the Spock character; however, Nimoy's stated intention was merely to remind the public at large that Spock and Nimoy were not one and the same. In the book, Nimoy conducts dialogues between himself and Spock.

His second autobiography was entitled I Am Spock (1995), and this title was meant to communicate that he finally realized that his years of portraying the Spock character had led to a much greater identification between the fictional character and the real person. Over the years, Nimoy had much input into how Spock would act in certain situations, and, conversely, Nimoy's contemplation of how Spock acted gave him cause to think about things in a way that he never would have thought if he had not portrayed this character. As such, in this autobiography Nimoy maintains that in some meaningful sense, he really is now Spock, and Spock is he, while at the same time maintaining the distance between fact and fiction.

Nimoy has also written several volumes of poetry, some published along with a number of his photographs. His latest effort is entitled A Lifetime of Love: Poems on the Passages of Life (2002). His poetry can be found in the Contemporary Poets index of The HyperTexts. In the mid '70s Nimoy wrote and starred in a one man play called Vincent based on the play Van Gogh by Phillip Stephens.

In 1995, Nimoy was involved in the production of Primortals a comic book series published by Tekno Comix that involved a first contact situation with aliens that had arisen from discussion between him and Isaac Asimov. There was a novelization by Steve Perry.

During and following Star Trek, Nimoy also released five albums of vocal recordings on Dot Records, including Trek-related songs and cover versions of popular tunes. The albums were extremely popular and resulted in numerous live appearances and promotional record signings that attracted crowds of fans in the thousands. The early recordings were produced by Charles Grean, who may be best known as the composer of "Quentin's Theme" for the mid-sixties goth soap opera, Dark Shadows. These recordings are generally regarded as unintentionally camp, though his tongue-in-cheek performance of "The Ballad of Bilbo Baggins" received a fair amount of airplay when Peter Jackson's The Lord of the Rings films were released.

In addition to his own music career he also directed a 1985 music video for The Bangles' "Going Down to Liverpool". He makes a brief cameo appearance in the video as their driver. This came about because his son Adam Nimoy (now a frequent television director) was a friend of Bangles lead singer Susanna Hoffs from college.

Starting in 1994, Nimoy began to narrate the Ancient Mysteries series on The History Channel including "The Sacred Water of Lourdes" and "The Last Days of the Romanovs". He also appeared in advertising in the United Kingdom for the computer company Time Computers in the late 1990s. He had a central role in Brave New World, a 1998 TV-movie version of Aldous Huxley's novel where he played a character wonderfully reminiscent of Spock in his philosophical balancing of unpredictable human qualities with the need for control. From 1999, during the run of the Futurama animation series, he featured in cameo voice-overs as either himself or Spock.

In 2003, he announced his retirement from acting in order to concentrate on his photography, such as his recent exhibit for nude pictures of BBW women, but has subsequently appeared in several popular television commercials with William Shatner for Priceline.com. He also appeared in a commercial for Aleve, an arthritis pain medication, which aired during the 2006 Super Bowl. Nimoy also provided a comprehensive series of voiceovers for the 2005 computer game Civilization IV. He also did the TV series Next Wave where he interviewed people about technology. He is the host in the documentary film The Once and Future Griffith Observatory currently running in the Leonard Nimoy Event Horizon Theater located at the recently reopened Griffith Observatory in Los Angeles, California. In January 2007, he granted an interview to Fat free film where he discussed his early career and the benefits of being type-casted.

Nimoy has long been active in the Jewish community, and is an adherent of Reform Judaism. One of his better-known roles was that of Tevye the milkman, in the musical Fiddler on the Roof, based on the series of short stories by Yiddish author Sholom Aleichem. In 1997 he narrated the documentary A Life Apart: Hasidism in America, about the various sects of Hasidic Orthodox Jews. In October 2002 Nimoy published Shekhina, a photographic study of women intended to visualize the feminine aspect of God's presence, inspired by Kabbalah (esoteric Jewish mysticism).

Nimoy has been married twice. In 1954, he married actress Sandra Zober, whom he divorced in 1987. He had two children by her, director Adam Nimoy and Julie Nimoy. In 1988, he married actress Susan Bay.

Nimoy came up with the Vulcan nerve pinch during the discussion of an early TOS episode ("The Enemy Within") where Spock was supposed to pistol-whip another character. He suggested the "pinch" as a non-violent alternative. Nimoy also devised the Vulcan Salute, a raised hand, palm forward with the fingers parted between the middle and ring finger. It is said to be based on the traditional kohanic blessing, which is performed with both hands, thumb to thumb in this position; a position thought to represent the Hebrew letter shin (ש). (This letter is often used as a symbol of God in Judaism, as it is an abbreviation for God's name Shaddai. This usage is seen, for example, on every mezuzah.) Nimoy may also have derived the accompanying spoken blessing, "Live long and prosper" from this source, as the last phrase of the blessing is "May the Lord be forbearing unto you and give you peace" (Numbers 6:24-26). Nimoy was asked to read the verses as part of his narration for Civilization IV.