[3][4] Her paternal grandfather, who played the accordion, mandolin and guitar, emigrated to the United States from Sicily; his surname was "Mercante" before it was anglicized.

[6] Merchant grew up Roman Catholic although she started drifting away from the faith as a teen but continues to believe in a God.

[12] She considered a career in special education after taking part in a summer program for disabled children, but in 1981, she started singing for a band, Still Life, which became 10,000 Maniacs.

[12] Merchant was lead singer and primary lyricist for 10,000 Maniacs, joining in its infancy in 1981 while she was a student at Jamestown Community College.

[13] Her last recording with the band, a cover of Bruce Springsteen's and Patti Smith's "Because the Night" at the 10,000 Maniacs MTV Unplugged performance, reached #11 on the Hot 100 chart on February 18, 1994; becoming the band's highest-charting song in the U.S.[14][15][16] After her split with 10,000 Maniacs, Merchant was so eager to begin writing her own material that she went home that very day and composed the song "I May Know the Word", which was originally meant to appear on the soundtrack to the Tom Hanks movie Philadelphia.

[2] The song was eventually cut from the soundtrack, but it would go on to appear on Merchant's debut solo album, Tigerlily, which was released on the Elektra label in 1995.

She did extensive touring for it and made numerous television appearances, including performances on Saturday Night Live, at the Rock and Roll Hall of Fame, and on late-night talk shows.

[22] The first single off the album was a happy and uncharacteristically simple song called "Kind and Generous", which received massive airplay on VH1 and which solidified Merchant's role as a bona fide solo artist.

That summer, Sarah McLachlan invited Merchant to co-headline the year's biggest music festival with her, Lilith Fair.

The exposure from the tour helped the album reach Platinum status in just under a year, with subsequent singles "Break Your Heart" and "Life Is Sweet" receiving moderate airplay on adult contemporary stations.

In 1998, Merchant also recorded George Gershwin's "But Not for Me" for the Red Hot Organization's compilation album Red Hot + Rhapsody, a tribute to George Gershwin, which raised money for various charities devoted to increasing AIDS awareness and fighting the disease.

The performance would be released as the album Natalie Merchant: Live in Concert with a companion video of the same name.

The performance was notable in that it featured numerous covers including songs by David Bowie, Neil Young, and Katell Keineg.

In 2000, Merchant embarked on a folk tour in the United States with many shows being supported by alt-country band Wilco.

[26] Her next studio album, The House Carpenter's Daughter, was released in September 2003 on her own label, Myth America Records.

Natalie Merchant was released May 6, 2014, on Nonesuch Records and was named Album of the Week by The Daily Telegraph.

[40] After suffering ossification of the posterior longitudinal ligament in 2019, Merchant received surgery for the condition, leaving her unable to sing for several months.

[41] In 2012, Merchant, along with actor and writer Mark Ruffalo, organized a concert to protest against oil and gas fracking in New York state.

A documentary, written and directed by Jon Bowermaster, was made of the event and titled Dear Governor Cuomo.

[42] She directed a short 2013 documentary titled Shelter: A Concert Film to Benefit Victims of Domestic Violence, that shone light on a group of women living in the mid-Hudson region of New York State responding to the crisis of domestic violence in their community with compassion and creativity.

It was inspired by an event for One Billion Rising, a global campaign calling for an end to violence against women, held on February 14, 2013.

Merchant presented a screening of the film at the Old Dutch Church in Kingston, New York, on the day of One Billion Rising for Justice.

[44] Merchant is a member of the Canadian charity Artists Against Racism and has worked with them in the past on awareness campaigns.