In 1964, he was suspended from school for "having long hair", and given money to get a haircut. Instead he went home, used the money for other things, and never returned to school.

Squire was fond of experimenting with LSD in the 1960s, until an incident where he had a bad acid trip. He recalled that "it was the last time I ever took it, having ended up in St Stephen's Hospital in Fulham for a couple of days not knowing who I was, or what I was, or who anybody else was." He also recalled that he spent months inside his girlfriend's apartment, afraid to leave, and it was during this time that he developed his style on the bass. He recovered and never used LSD again.

Squire's first bass was a Futurama, "very cheap, but good enough to learn on." His early influences were diverse, ranging from church and choral music to the Merseybeat sounds of the early 1960s and he studied the bass styles of John Entwistle, Jack Bruce, and Larry Graham. Squire's first musical groups The Selfs, The Syn (both including Jackman), and later, Mabel Greer's Toyshop, would introduce him to his early Yes collaborators Peter Banks and Jon Anderson. In 1965, he made his first public appearance with the Selfs at "The Graveyard" youth club in St Andrew's Church Hall.

During his first conversation with Anderson, the pair broke the ice by discussing one of their favourite groups, Simon & Garfunkel (Yes later covered the duo's "America") and Squire discovered that he and Anderson were both into vocal groups. Squire claimed Yes was formed with Anderson, drummer Bill Bruford and keyboardist Tony Kaye partly out of necessity. "I couldn't get session work because most musicians hated my style. They wanted me to play something a lot more basic. We started Yes as a vehicle to develop everyone's individual styles."

Yes released their first record in 1969, and though the band have had many personnel changes over the years, they have continued to record and tour for nearly 40 years. Squire is the only original member who has remained in the lineup throughout the band's recording tenure, with Jon Anderson only having been absent on Drama. He has also been one of the main forces behind the band's music. While Anderson typically handled the lyrics, Howe and Squire co-wrote much of the band's music with Anderson. In addition, Squire and Howe would supply backing vocals in harmony with Anderson, which can be heard on songs like "South Side of the Sky" and "Close to the Edge".

During the band's formative years Squire was frequently known for his tardiness, a habit that drummer Bill Bruford often complained about. Because of this, Squire would frequently drive at unsafe speeds to get to gigs on time, once causing a horrific accident on the way to a gig in West Germany after he fell asleep at the wheel, although miraculously nobody was injured.

As Squire, along with Alan White and Steve Howe, co-owned the "Yes" name at the time, the 1989 ABWH lineup without him (which contained Anderson, Bruford, Wakeman and Howe) could not record under that name.

Squire has concentrated overwhelmingly on Yes' music over the years, and his solo works have been few and far between. His first and only true solo record was 1975's Fish Out of Water, featuring Yes alumni Bill Bruford on drums and Patrick Moraz on keyboards and The Syn/The Selfs alumnus Andrew Jackman also on keyboards. Squire was later a member of the short-lived XYZ (eX-Yes/Zeppelin) in 1981, a group composed of Alan White (Yes) on drums and Jimmy Page (Led Zeppelin) on guitar. XYZ recorded several demo tracks at Squire's home studio in Virginia Water, but never produced anything formal (ostensibly because vocalist Robert Plant, still mourning for John Bonham, failed to get interested). XYZ never officially released any material, though two of the demos provided the basis for two later Yes tracks, "Mind Drive" and "Can You Imagine?". Squire also played a role in bringing Trevor Rabin into the Cinema band project, which became the 90125 lineup. Later, Squire would join with Yes guitarist Billy Sherwood in a side project called Conspiracy. This band's self-titled debut album contained the nuclei of several songs that had appeared on Yes' recent albums. Conspiracy's second album, The Unknown, was released in 2003.

In late 2004, Squire joined a reunion of The Syn, subsequently leaving the band in May 2006. He is now working on two solo projects with other former Syn collaborators Gerard Johnson, Jeremy Stacey and Paul Stacey. A Christmas album, Chris Squire's Swiss Choir, was released in 2007 (with Johnson, J. Stacey and Steve Hackett).

On 9 February 2009, Squire was rushed to a hospital for an aneurysm in his leg leading ultimately to the cancellation of the remaining dates of a part of the In the Present tour. He has since fully recovered and touring resumed.

Squire's bass playing is noted for being aggressive, dynamic, and melodic. Squire's main instrument is a Rickenbacker bass (model RM1999, serial number DC127), which he has owned and played since 1965—the year it was first introduced. In many ways, the Rickenbacker was the polar opposite of the then commonly used Fender bass. (In fact, the electric bass at the time was often referred to as the "Fender.") The RM1999 was a budget, monophonic version of Rickenbacker's 4001 stereo bass. This model was imported into the UK by Rose Morris Ltd (hence the RM prefix on the model number) and, according to Squire's official website, was only the fourth bass of its type to be imported into Britain from the United States. Squire mentioned in a 1979 interview with Circus Weekly that he acquired this bass while working at the Boosey & Hawkes music store in London. This instrument, with its warmth and distortion, is a significant part of Squire's unique sound. Due to its distinct high/mid tone it allowed the bass to take on a more "lead" role which suited Squire perfectly. Unlike the grooving low end thump established by James Jamerson and imitated throughout the world of rock and R&B, Squire constructed contrapuntal lines reminiscent of a "Bach/Baroque" style where the bass played a separate melody from the main theme. The fact that the Rickenbacker had a "harpsichord-like" sound suited this approach perfectly.

According to his interview in Guitar Player magazine in October 1973, Squire obtained his distinctive tone at the time by rewiring his RM1999 into stereo and sending the bass and treble pickups each into a separate amplifier. By splitting the signal from his bass into dual high and low frequency outputs and then sending the low frequency output to a conventional bass amplifier and the high-frequency output to a separate lead guitar amplifier, Squire produced a tonal 'sandwich' that added a growling, overdrive edge to the sound while retaining the Rickenbacker's powerful bass response. This gave his bass sound bright, growling higher frequencies and clean, solid bass frequencies. This technique allowed Squire to utilize harmonic distortion on his bass while avoiding the flat, fuzzy sound, loss of power and poor bass response that typically occurs when bass guitars are overdriven through an amplifier or put through a fuzz box. He also plays with a pick which contributes to the sharp attack as well as using fresh Rotosound Swing Bass strings for every show.

Chris Squire is commonly known by his nickname "Fish", and the name is associated with many of his works (including his solo record, Fish Out of Water, and the solo piece "The Fish (Schindleria Praematurus)" from the 1972 Yes record Fragile). The name has multiple origins. First, his astrological sign is Pisces, and he is apparently a believer in astrology. Second, in the early days of Yes' career, he once accidentally flooded a hotel room in Oslo, Norway, while taking a shower, and Bill Bruford gave him the nickname. He may also have acquired this nickname because of the alleged amount of time he spends in the bath tub. On the 2007 documentary "The Classic Artists Series 3: Yes", Bruford says that the nickname arose because Squire spent long periods in the bathroom while they shared a house together in Fulham.

Chris Squire married Nikki in the 1970s. Nikki sang on the 1981 Christmas single "Run with the Fox" and also the track "Hold Out Your Hand" from Fish Out Of Water and later had her own band, Esquire, on whose first album Chris, Alan White and Trevor Horn assisted. Their family included Carmen Squire (Chris's stepdaughter), Chandrika and Camille Squire. Chris and Nikki divorced after fifteen years. Chris then married actress Melissa Morgan on 8 May 1993, they have a son, Cameron. The two have since divorced. He is now married to his third wife, Scotland, who gave birth to their first child, a daughter named Xilan, on 19 December 2008. They reside in the Chelsea neighbourhood of London.
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Christopher Russell Edward "Chris" Squire (born 4 March 1948), is an English musician best known as the bass guitarist and backing vocalist for the progressive rock group Yes. He is the only member of the group to appear on every album (with the exception of the Anderson Bruford Wakeman Howe material.) He is well known for his technical virtuosity and a melodic "Bach/Baroque" sound.

He was born in Kingsbury, a suburb of northwest London, in England. His father was a cab driver and his mother a housewife. He was trained in the St Andrew's church choir as a young boy, beginning his musical career in the church's basement, along with his friend Andrew Jackman. When Squire was about sixteen, The Beatles and Paul McCartney were the catalyst that prompted him to consider a career in music and to take up the bass guitar.