Kerr came to prominence in the early 1990s via a musical partnership with fellow fiddle player Eliza Carthy. The duo produced two albums - Eliza Carthy & Nancy Kerr (1993) and Shape of Scrape (1995) - before ceasing to work together. A retrospective collection of their work (plus three previously unreleased tracks) - On Reflection - was released in 2002.
Kerr and her mother released an album together - Neat and Complete - in 1996.
Since 1995 Kerr has worked extensively with Australian bouzouki player and singer James Fagan, whom she married in 2007. The duo won the Horizon Award at the inaugural BBC Radio 2 Folk Awards in 2000, and Best Duo at the same awards in both 2003 and 2011. Between 1997 and 2008 they released six albums on the Fellside label - Starry Gazy Pie, Scalene (with Sandra Kerr) , Steely Water, Between The Dark and Light, Strands of Gold and Station House (with Robert Harbron). The album Station House was the result of a collaboration with concertina player Robert Harbron to form the trio Kerr Fagan Harbron. In 2010 Kerr and Fagan produced their first completely original collection of songs - Twice Reflected Sun. The first track of the album, Queen of Waters, was nominated for the "Best Original Song" category at the BBC Radio 2 Folk Awards in 2011.
Kerr has also worked with a number of groups, including folk/pop group Epona, Australian folk family band The Fagans and the Tim van Eyken band. In 2010 she joined James Fagan, Richard Arrowsmith and Jess Arrowsmith to form Melrose Quartet in her new home city of Sheffield. They released a live EP in 2011 called Live at Cheltenham and two studio albums: Fifty Verses in 2013 and Dominion in 2017. She has also performed in the trio Simpson Cutting Kerr, with Martin Simpson and Andy Cutting, whose debut CD Murmurs was released on Topic Records on 8 June 2015.
Kerr has been involved in several commissioned works. In 2013 she was part of Fay Hield's The Full English band to promote the on-line publication of the folk collections of the Vaughan Williams Memorial Library in Cecil Sharp House. The collective won "Best Group" at the 2014 BBC Radio 2 Folk Awards and their CD The Full English won "Best Album" at the same ceremony. In 2014 Kerr was a key songwriter in The Elizabethan Session, a concert, CD and film commissioned by Folk By The Oak and The English Folk Dance and Song Society creating new music about the Elizabethan era. In November 2015, Kerr was one of four songwriters commissioned by Folk By The Oak and The English Folk Dance and Song Society to write and tour a production called Sweet Liberties looking at the history of British parliament and democracy. Their CD Sweet Liberties was released in 2016. In 2017 and 2018 Kerr was one of five musicians who formed Shake the Chains, a project that explored "the role songs have played in social change, resistance and protest". The project was commissioned by Folk by the Oak and supported by Arts Council England, Help Musicians and Folk Alliance. The group toured in 2017 and 2018, and made a live album in 2017.
In 2014, Kerr released Sweet Visitor, her first CD of original songs under her own name, on her own label Little Dish Records. The album's release on 21 July 2014 was followed by a UK tour with The Sweet Visitor Band (James Fagan, Rowan Rheingans, Tom Wright and Tim Yates) in November. James Fagan now shares his role in the band with Greg Russell. 2016 saw the production of Kerr's second album of original songs with The Sweet Visitor Band on Little Dish Records. The album, entitled Instar, was produced by Tom Wright and was released on 16 September 2016.