He began playing at 13, his primary influences then being Hank Marvin of The Shadows and Django Reinhardt. Although his father was a jazz pianist, he was primarily self-taught. By the time he joined his first notable band, Rush Release (including future Gracious! drummer Robert Lipson), his influences were Peter Green, Jeff Beck and, later, Jimi Hendrix. The band played at London's Speakeasy Club ca. 1966, on occasion jamming with such luminaries as Eric Clapton. Between 1967-70, Etheridge's studies (history of art at Essex University) took him away from the London scene. A crucial discovery for him during this period was John McLaughlin's debut album Extrapolation.
Back in London, Etheridge briefly worked with the Deep Purple offshoot Warhorse, followed by a stint with Icarus, during the final stages of recording their album The Marvel World Of Icarus. He recalled "I'd been on the fringes of the London rock scene for a couple of years, and one of the musicians I came across was [Icarus woodwinds player] Norrie Devine. I desperately needed somewhere to live, and he put me in touch with Peter Curtain." Curtain, also the drummer for Icarus, set Etheridge up with a flat and offered him a spot in the band after their guitarist left. Though the album sleeve credited Etheridge for all the guitar parts, in fact only one track featured him as the sole guitarist, though he did overdubs on several other tracks. He stayed with Icarus for their subsequent tour of Romania, which ended abruptly when President Nicolae Ceaușescu ordered the band to be deported, and proved to be their final public appearance.
In 1971 he helped form Abednego, which broke up after a year having failed to secure a recording contract. In late 1972, he joined Curved Air violinist Darryl Way's band Wolf, which went on to record three albums in the progressive rock canon for the Deram label, Canis Lupus (1973), Saturation Point (1973) and Night Music (1974). It also provided an outlet for his first compositions, at a rate of one or two on each album.
Wolf's break-up was followed by a brief interim in the Global Village Trucking Company for a UK tour supporting Gong in early 1975, before a recommendation from fellow guitarist Allan Holdsworth led to him joining Soft Machine, now in full fusion mode having just released Bundles. Etheridge went on to record two albums with the band, Softs (1976) and Alive & Well: Recorded in Paris (1978). He also played on the more recent British Tour 1975.
With Soft Machine's activities slowing down and ultimately (by 1978) stopping completely, Etheridge developed parallel ventures, including a long-term collaboration with French violin legend Stéphane Grappelli (numerous world tours from 1976–81), and the band 2nd Vision with fellow Soft Machine member, violinist Ric Sanders, which released a self-titled album in 1980, but fell victim to the hostile post-punk environment and broke up in 1981.
The 1980s saw Etheridge remain very active on the live front (including a reunion with Soft Machine for the band's final series of concerts at Ronnie Scott's club in 1984), but much less so in the studio. "1981 was a sort of watershed year for me... there's sort of before and after 1981. Since then I've mostly played on my own or led bands, playing alongside other people but not in settled formations. That was partly because I liked to do that, and partly because, frankly, I didn't really know what to do with myself at that point. I'd always enjoyed playing sort of jazz-type gigs, so I started doing it..."
In 1982, Etheridge played solo concerts in Australia and duo dates with bassist Brian Torff in the US. In 1984 he toured England with his own trio, and the following year joined forces with ex-Isotope guitarist Gary Boyle. Between 1989 and 1993, he was a member of Danny Thompson's group Whatever, playing on the album Elemental (1990). Between 1988-94, he did a lot of touring in Germany with Dick Heckstall-Smith, recording two albums as the Dick Heckstall-Smith / John Etheridge Band, Live in Erlangen and Obsession Fees. Also in 1988 he made a duo record with New York guitarist Vic Juris, Bohemia, toured with Biréli Lagrène, and played in the Elton Dean/John Etheridge Quartet with Fred Baker (bass) and Mark Fletcher (drums). In 1992, he joined violinist Nigel Kennedy's live band, playing on his albums Kafka (1996) and The Kennedy Experience - The Music Of Jimi Hendrix (1999).
In 1994, he released a duo album, Invisible Threads, with longtime friend Andy Summers (also a former Soft Machine guitarist, albeit in a much earlier incarnation of the group), and did a world tour with him. The duo recorded the album using only acoustic guitars and acoustic bass. The same year, Etheridge released his first solo album, Ash, mostly featuring his regular band at the time - Steve Franklin on keyboards, Henry Thomas on bass and Mark Fletcher on drums - as well as duets with bassist Dudley Phillips. Subsequent solo albums included Chasing Shadows (2000), I Didn't Know, Stitched Up (2006, with his Trio North), In House - Live In London (2007, with Arild Andersen and John Marshall), Alone - Live ! (2008) and Break Even (2008, with Liane Carroll).
In addition to countless one-off line-ups assembled for jazz gigs, Etheridge is involved in several long-term projects: a guitar duo with John Williams, which released Live In Dublin - Places Between; the Grappelli tribute Sweet Chorus, which released Sweet Chorus - Tribute to Grappelli in 1998; the Frank Zappa tribute band Zappatistas (formed 1999), who released a live CD, The Music Of Frank Zappa - Absolutely Live (2001) and have since toured widely, appearing at the German progressive rock/jazz festival Zappanale in 2006; and Soft Machine Legacy, alongside fellow ex-Soft Machine members Hugh Hopper, John Marshall and Elton Dean (the latter replaced by Theo Travis after Dean died in early 2006). They have so far released two studio albums (both including Etheridge compositions), Soft Machine Legacy (2005) and Steam (2007), and two live releases, Live in Zaandam (2005) and Live At The New Morning (2006), the latter also a DVD, filmed just weeks prior to Dean's passing.