Cline began to play guitar at age 12 when his twin brother, Alex Cline took up the drums. He is noted for his use of effects pedals and looping devices which give his music a distinct sound. The brothers graduated from University High School (Los Angeles, California).
Cline is known for his improvisational work and for the diversity of his musical projects. He has played with jazz musicians Charlie Haden, Gregg Bendian, Wadada Leo Smith, Tim Berne, Vinny Golia and the late bassist Eric Von Essen, a longtime musical companion in the L.A. jazz group Quartet Music.
Cline has also performed and recorded with punk rock hero Mike Watt in his touring bands The Crew of the Flying Saucer and The Black Gang, as well as with members of Sonic Youth and country music legend Willie Nelson, and in the jazz/punk/improv band Banyan with Watt and ex-Jane's Addiction drummer Stephen Perkins. He frequently participates in jazz projects with his twin brother, Alex, however their first actual duo together was in Culver City, California, during their 50th birthday show.
Nels's first appearance on an album was on Vinny Golia's 1978 record, Openhearted, and his first work as a bandleader was 1988's Angelica. In the late 1980s, Cline formed the Nels Cline Trio, which featured his guitar playing complemented by Mark London Sims at bass and Michael Preussner at drums. The trio released several 7 inch demos and one album, before replacing Sims with Bob Mair at bass. This new trio released three albums before splitting up, featuring some of Cline's most melodic works, before he ventured into a freer and more minimalist territory in the decade to come. Shortly before the end of the trio, Nels recorded two albums, In-Store, and Pillow Wand, with Sonic Youth frontman and guitarist, Thurston Moore.
Nels was also a member of the Geraldine Fibbers with then-partner Carla Bozulich
In 1999, Cline paired up with jazz drummer Gregg Bendian to record a modern rendition of John Coltrane's 1967 album, Interstellar Space. On Interstellar Space Revisited: The Music of John Coltrane, Bendian and Cline reinterpret Coltrane's piece using their own distinctive approaches. He also participated in ROVA's Electric Ascension (2005), a performance of Coltrane's landmark large-ensemble recording Ascension (1965).
Cline's current outfit is the improv/free jazz ensemble The Nels Cline Singers, with which he has recorded three albums, Instrumentals, The Giant Pin and Draw Breath, his most recent work as a leader. The Nels Cline Singers are currently signed with Cryptogramophone Records.
Another important project of Cline's has been the Acoustic Guitar Trio, a free-improvisation group with Jim McAuley and the late Rod Poole that specialized in microtonal improvisation.
Cline has performed on over 100 albums in the jazz, pop, rock, country, and experimental music genres. He continues to expand his audience as a member of the Grammy-winning rock band Wilco, which he joined in early 2004. He was later featured in the cover story of Guitar Player Magazine for his newfound collaboration with the band.
In February, 2007, Cline was chosen by Rolling Stone Magazine as one of the Top 20 New Guitar Gods given the title "The Avant Romantic".
Nels Cline appears on Wilco's 2007 album, Sky Blue Sky, as well as the live album "Kicking Television: Live in Chicago," and is currently touring with the band.