The media have sometimes labeled her as one of the most prominent members of the modern psych folk movement. Newsom, however, claims no ties to any particular music scene. Her songwriting incorporates elements of Appalachian music and avant-garde modernism.

She was exposed to music from a young age. Her father played the guitar and her mother was a classically trained pianist who played the hammered dulcimer, the autoharp and conga drums. Newsom attended a Waldorf school where she studied theater and learned to memorize and recite long poems. This skill helps her to remember lyrics while on tour.

At the age of five, Newsom asked her parents if she could play the harp. Her parents eventually agreed to sign her up for harp lessons, but the local harp instructor did not want to take on such a young student and suggested she learn to play the piano first. Starting at the age of four she began playing the piano. Only later did she move on to the harp, which she, "loved from the first lesson onward."

From her instructor, Joanna learned composition and improvisation. She first played on a smaller Celtic harps until her parents bought her a full-size pedal harp in the seventh grade.

After high school Newsom studied composition and creative writing at Mills College in Oakland, California. While at Mills, she played keyboards in The Pleased. She dropped out of the school in order to focus on her music.

In 2002 and 2003, Newsom recorded two EPs, Walnut Whales and Yarn and Glue. These homemade recordings were intended to serve as a document of her early work; she recorded them on a Fisher-Price tape recorder. These EPs were not intended for public distribution. At the suggestion of Noah Georgeson, her then-boyfriend and recording engineer of the EP, she burned several copies to sell at her early shows. John Fellman, co-producer of Mission Creek Music and Arts Festival, claims to be the first to have booked a show for her.

A friend of Newsom's passed one of these CDs on to Will Oldham at a show in Nevada City. Oldham was impressed with Newsom's music and asked her to tour with him. He also gave a copy of the CD to the owner of Drag City, his record label. Drag City signed Newsom and released her debut album The Milk-Eyed Mender in 2004. Shortly thereafter, Newsom toured with Devendra Banhart and Vetiver and made an early UK appearance at the Green Man Festival in Wales, returning to headline in 2005, 2007 and 2010.

Her second album Ys was released in November 2006. The album features orchestrations and arrangements by Van Dyke Parks, engineering from Steve Albini and mixing by Drag City label-mate Jim O'Rourke.

Newsom is known to debut songs impromptu at her concerts. On March 28, 2009, she performed over two hours of new material at a 'secret' concert in Big Sur, California with fellow Nevada City singer-songwriter Mariee Sioux under the pseudonym 'The Beatles's'. Those in attendance reported that about one-third of her new material was played primarily on piano, with a backing arrangement of banjo, violin, guitar and drums.

Since late 2006, Newsom has performed a solo harp version of the traditional Scottish song "Ca the Yowes Tae the Knowes".

Several of the songs on The Milk-Eyed Mender have been covered by her peers. "Bridges and Balloons" was covered by The Decemberists on their 2005 EP Picaresqueties. "Sprout and the Bean" has been covered by The Moscow Coup Attempt and Sholi. "Peach, Plum, Pear" has been covered by Final Fantasy (Owen Pallett) on the 2006 EP Young Canadian Mothers, as well as by Straylight Run. M Ward has played "Sadie" at some of his live shows.

On February 11, 2010, Pitchfork Media reported that Newsom would be the subject of a tribute book titled Visions of Joanna Newsom which has now been published by Roan Press.She toured throughout Europe and America in 2010 to promote her latest record, supported by a five-piece band. In December 2010, a tribute album of Newsom covers was released as a digital download. Artists involved include M. Ward, Billy Bragg, Guy Buttery and Owen Pallett, with all proceeds going to Oxfam America's Pakistan Flood Relief Efforts.

Newsom was also chosen by Jeff Mangum of Neutral Milk Hotel to perform at the All Tomorrow's Parties festival that he curated in March 2012 in Minehead, England.

In late 2011, Newsom contributed vocals to "The Muppet Show Theme" for The Muppets and appeared on the cover of the 10th anniversary issue of Under the Radar with Robin Pecknold.

Newsom began 2012 with television appearances on Austin City Limits (on January 21) and Portlandia (on February 7). On June 25, 2012, Newsom performed at the Warfield Theatre in San Francisco with Philip Glass and Tim Fain as part of a benefit for the Henry Miller Memorial Library.She performed a new song at the concert tentatively "The Diver's Wife", a love story concerning pearl hunting.

Newsom appeared on a track titled "Kindness be Conceived" on Thao and the Get Down Stay Down's album We The Common, released in February 2013.In March 2013, Newsom contributed to the song "The Man Who Ran The Town" on the Hard Skin album Why Do Birds Suddenly Appear.

Also in March 2013, Newsom participated in a short film for Melissa Coker's Wren clothing line. In the film, Newsom wears Wren clothing and performs a cover of Sandy Denny's "The North Star Grassman and the Ravens".

Newsom's early work was strongly influenced by polyrhythms. Her harp teacher, Diana Stork, taught her the basic pattern of four beats against three which creates an interlocking, shifting pattern that can be heard on Ys, particularly in the middle section of "Sawdust & Diamonds." After Ys, Newsom said she had lost interest in polyrhythms. They "stopped being fascinating to me and started feeling wanky."

She appeared in, and narrated, the 2014 film Inherent Vice, directed by Paul Thomas Anderson. Peter Travers of Rolling Stone called Newsom's narration in the film "gorgeously rendered." In 2015, she provided additional vocals for The Lonely Island's songs "Ras Trent" and "We Are a Crowd". Divers, her fourth solo record, was released on October 23, 2015. The album peaked at number one on the Billboard Alternative Albums chart, and outsold her previous record, Ys (2006). On December 8, 2015, she performed "Leaving the City" from the album on The Late Show with Stephen Colbert.

Newsom's vocal style (in the November 2006 issue of The Wire she described her voice as "untrainable") has shadings of folk and Appalachian shaped-note timbres.

In addition to her solo work, Newsom has played on records by Smog, Vetiver, Nervous Cop, The Year Zero, Vashti Bunyan, Moore Brothers, Sydney Symphony Orchestra, Golden Shoulders and The Roots and played keyboards for The Pleased.

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