Early career & The Bicycle Thief (1995-2001)Dropping out of formal education at age of 15, Klinghoffer became involved in performing and recording music in Los Angeles at an early age. Klinghoffer describes himself at this time as "[the] little music dork who lived around the corner, dropped out of high school, and was just playing guitar all day long." In 1997, at the age of seventeen, Klinghoffer joined The Bicycle Thief, the then-current project from former Thelonious Monster frontman Bob Forrest. Red Hot Chili Peppers vocalist Anthony Kiedis noted that, "Bob [Forrest] has always had a very keen sensibility about finding extremely talented and down-to-earth people who just want to get to a kitchen and write a song." The band's subsequent studio album, You Come and Go Like a Pop Song, marked Klinghoffer's first recording experience. Regarding bandmate Forrest's notorious drug addiction, which arguably stalled Thelonious Monster's commercial success, Klinghoffer stated at this time that he: "Pretty much had enough confidence in myself to know that I wasn't gonna be 'the next Bob Forrest'."
In 2000, The Bicycle Thieves opened for Red Hot Chili Peppers, as they toured in support of their seventh studio album, Californication.
 John Frusciante and Ataxia (2002-2004)Klinghoffer and then-Red Hot Chili Peppers guitarist John Frusciante began writing together in 2002, with the hopes of recording and releasing an album under a band name. This album was eventually released as a John Frusciante solo release in 2004, entitled Shadows Collide with People. Regarding this decision, Frusciante stated:
|“||We had written the song "Omission" together and this song came about through collaboration. He played keyboard and I played guitar and both of us had the ideas for the vocals. [...] We sat there and scribbled our parts onto a piece of paper and when we were ready we got back together again and sung our ideas together and they fit perfectly. At that time we thought that we'd do many songs together, just like this one. As time went by, this album became more of a solo album with which he's helping me. [...] We'll do further projects where we'll work together, but we realized that these were my songs and it therefore had to be a solo album.||”|
In 2004, Klinghoffer also appeared on former bandmate Bob Forrest's latest studio album with Thelonious Monster, California Clam Chowder.
 Stadium Arcadium tour and Dot Hacker (2007-2009)In 2007, Klinghoffer joined Red Hot Chili Peppers on the final few legs of their Stadium Arcadium tour, performing additional guitar, backing vocals, and keyboard parts alongside the band. This tour would ultimately be John Frusciante's last with the band, and coincidently Klinghoffer's first.
Klinghoffer founded his own band, Dot Hacker, in 2008, where he holds the position of primary songwriter, singer, rhythm guitarist and pianist. To date, they have released four songs, "Order/Disorder", "Eye Opener", "Neon Arrow" (via their my space) and "Inhibition" which was played in a Bob Forrest's radio show on the Los Angeles. 
On May 8, 2009, amidst confusion as to whether Frusciante still remained within Red Hot Chili Peppers, Klinghoffer, Anthony Kiedis, Flea, Chad Smith, Ron Wood and Ivan Neville performed under the name, The Insects, at a MusiCares in honour of Kiedis's commitment to helping those struggling with addiction and recovery.
 Joining Red Hot Chili Peppers (2009)On October 12, 2009, the Red Hot Chili Peppers ended a two-year hiatus, and were joined by Klinghoffer in the studio to begin work on their tenth album. On January 29, 2010, Klinghoffer performed with the band for the first time as their lead guitarist at a MusiCares tribute event to Neil Young for a performance of Young's "A Man Needs a Maid." It was later revealed he would permanently replace Frusciante as guitarist. Klinghoffer was officially named the replacement for John Frusciante in early 2010. Regarding his entry into the band, Klinghoffer notes, "I've always been attracted to the idea of a tight-knit unit, a band of family, a brotherhood. Since my earliest memory, they always seemed like a band with a lot of love for each other."
In May 2010, Klinghoffer along with Flea performed the United States national anthem at a Lakers home playoff game during the NBA Western Conference Finals series against the Phoenix Suns.
After eleven months of writing and rehearsing, the Chili Peppers began recording their new album on September 13, 2010. According to drummer Chad Smith, Klinghoffer also sang, wrote music and played keyboards on the upcoming album. Recording for the new album was completed on March 18, 2011 and was in the process of being mixed. The album, now called I'm with You, was released on August 29, 2011. The band's first single off the new album, "The Adventures of Raindance Maggie", features intricate, textured, and layered guitars and Klinghoffer's unique style and guitar playing has clearly taken the band in a new musical direction.
In 2011, Klinghoffer wrote and performed the original score for the documentary Bob and the Monster. Klinghoffer also appears in the documentary, which is based on the life and career of musician and drug counselor Bob Forrest.
Klinghoffer will also appear on former Jane's Addiction bassist Eric Avery's forthcoming solo album.
On July 10, 2011, Klinghoffer appeared at the 2011 School of Rock's Rock the House Tour which also featured Keith Morris and Page Hamilton. Klinghoffer joined the School of Rock kids on stage to perform Red Hot Chili Peppers songs "Dani California' and "Give It Away". This was the first time he performed any of the Chili Peppers' songs live since officially joining the band as their guitarist
Klinghoffer has played a 3-tone Sunburst Fender Telecaster (previously owned by John Frusciante), an Eastwood Airline '59 Custom 3P, a 3-tone Sunburst Fender Stratocaster, a Vintage Sunburst Gibson Firebird VII, a Cherry Red Gibson ES-335, and a Gretsch White Penguin during I'm with You Tour.
Klinghoffer uses two or three amps on stage, a Fender Super Reverb combo for clean tones (super six reverb), a Marshall JCM 800(2210) half stack for the distorted tones, and occasionally a vintage Silvertone stack.
- EHX Nano Holy Grail Reverb, BOSS DD-6 Digital Delay, EHX Freeze, EHX Cathedral Reverb, BOSS PS-5 Super Shifter, MOOGER FOOGER 12-Stage Phaser, IBANEZ WH-10 Wah, XOTIC EP booster, MXR Distortion +, MXR Micro amp, TAKE FLIGHT Gooze fuzz, BOSS DM-2 Analog Delay, BOSS DD-7 Delay, BOSS CE-2, BOSS CS-2 Compressor, EHX Memory man tap tempo, EHX Memory boy, EHX Memory man, BOSS TU-2 Tuner, MOOGER FOOGER Low-Pass Filter, MOOGER FOOGER EP2 Expression Pedal, MOOGER FOOGER EP2 Expression Pedal, L.A.L. NOISE CYBER PSYCHIC parametric oscillo filter, LINE 6 FM4,
 Personal lifeJosh is distantly related to Leon Klinghoffer who was murdered by terrorists aboard Achille Lauro in 1985. According to Josh, Leon was a fourth or fifth cousin of his grandfather.
- A Sphere in the Heart of Silence (2004) (credited to both John Frusciante and Josh Klinghoffer)
- I'm With You (2011)
- with The Bicycle Thief
- with Ataxia
- with John Frusciante
- Shadows Collide With People (2004)
- The Will to Death (2004)
- Inside of Emptiness (2004)
- The Empyrean (2009)
- with Warpaint
- Exquisite Corpse (2008)
- with Golden Shoulders
- Let My Burden Be (2002)
- Friendship Is Deep (2004)
- Get Reasonable (2009)
- Other appearances
- Pop Killer - Paul Oakenfold (2010) 
- Bambi Lee Savage – "GJ and the PimpKillers" (2009)
- The Last Laugh - Joker's Daughter (2009)
- The Silence of Love - Headless Heroes (2008)
- Chains- Pocahaunted (2008)
- The Blue God - Martina Topley-Bird (2008)
- The Odd Couple- Gnarls Barkley (2008)
- Stainless Style - Neon Neon (2008)
- The Deep Blue - Charlotte Hatherley (2007)
- Nun Lover! - Spleen (2007)
- A Loveletter to the Transformer, Pt. 1 The Diary of IC Explura (2007)
- The Peel Sessions 1991-2004 - PJ Harvey (2006)
- Dog Problems - The Format (2006)
- Modern Folk and Blues: Wednesday - Bob Forrest (2006)
- The Roads Don't Love You - Gemma Hayes (2005)
- California Clam Chowder - Thelonious Monster (2004)
- Blowback - Tricky (2001)
- Song Yet to be Sung - Perry Farrell (2001)
- The Bicycle Thief (Guitar, 2000)
- Vincent Gallo (Guitar, Bass, Piano, 2001)
- Butthole Surfers (Guitar, 2001)
- Beck (Guitar, 2003)
- Golden Shoulders (Bass, 2003)
- PJ Harvey (Guitar, 2004)
- Sparks (Guitar, 2006)
- Gnarls Barkley (Guitar & Synthesizer, 2006–2008, Vocals, 2008)
- Red Hot Chili Peppers (Guitar, Vocals, Synthesizer, Drums & Percussion, 2007)