Chinyere Nnenna Pierce was born on July 28, 1954, in Cambridge, Massachusetts, to Charles and Frances Pierce, and grew up there with a brother, Melvin, and a sister, Debbie. She sang in her neighborhood and in church, at Union Baptist and at St. Paul AME, and heard Sarah Vaughan, Nina Simone and Billy Eckstine on her parents' record player. She has been careful, in interviews, to credit a set of local singers nobody outside Cambridge ever heard of alongside the famous ones. Music was not the plan. She took a degree in health care administration at Simmons College in Boston, moved to North Carolina, and went to work for the Durham County Hospital Corporation. In 1979 she married the architect Philip Freelon, who would later lead the design team for the Smithsonian's National Museum of African American History and Culture, and the couple raised three children in Durham. She sang locally through all of it, following a piece of advice from her grandmother she has quoted for forty years since: bloom where you are planted, sing where you are, do not get on a bus to New York.

The break came in 1990, at a Southern Arts Federation jazz meeting, where she met the pianist and educator Ellis Marsalis. Marsalis was scouting for Dr. George Butler at Columbia Records, who was looking for a female singer; he asked for a tape, she handed over a local press kit and a cassette of original material, and two years later she had a Columbia contract. She was thirty-seven when Nnenna Freelon came out in 1992, with Ron Carter, Buster Williams, Grady Tate and Gene Bertoncini on it and a full string section behind her. Reviewers heard too much Vaughan in it, a debt AllMusic lays at the producer's door rather than the singer's. Heritage followed in 1993 with Kenny Barron, Christian McBride and Lewis Nash, and Listen in 1994, cut at Sear Sound over a week that February and March with Yusef Lateef playing alto flute on it. Lateef had been her teacher, and she had built her phrasing by listening to horn players rather than to other singers. Columbia dropped her the same year.

Concord signed her in 1995 and gave her the artistic control Columbia had not. Shaking Free arrived in 1996 and brought her first Grammy nomination. Maiden Voyage, recorded at Sound On Sound in New York across three days in September and October 1997, was the record that fixed her reputation: twelve songs organized around women's writing and women's lives, from Nina Simone's "Four Women" to Sippie Wallace's "Women Be Wise" to a Laura Nyro tune, with Herbie Hancock playing piano on the title track he had written thirty-two years earlier. The Israeli bassist Avishai Cohen, then in Chick Corea's Origin and appearing courtesy of Corea's Stretch label, holds the bass chair on seven of the twelve tracks, with Peter Washington on three more. It was nominated for a Grammy in 1999.

The Concord decade that followed was her most productive. She produced Soulcall herself in 2000, recorded over three April days in New York with Chris Potter, Ed Thigpen, Ray Drummond and James Williams among the players and Take 6 and Sounds of Blackness guesting, and it drew two nominations at once, for the album and for the arrangement of "Button Up Your Overcoat." The same year she made her acting debut in the film What Women Want. Tales of Wonder in 2002 was a Stevie Wonder songbook record with Dave Samuels and Gerry Niewood in the band, and it charted higher than anything else she has made. Live captured two February nights at the Kennedy Center in 2003. Blueprint of a Lady: Sketches of Billie Holiday, cut at Fantasy Studios in Berkeley in the spring of 2005 with the young Julian Lage on guitar and Christian Scott on trumpet, took the Holiday songbook apart and rebuilt it in contemporary settings, which delighted some critics and annoyed others; it was nominated at the 2006 ceremony. Through the same years she was the only singer in the Monterey Jazz Festival 50th Anniversary All-Stars, the touring band assembled for the festival's fiftieth season in 2007 alongside Benny Green, James Moody and Terence Blanchard. She had already sung at the White House the year before, on September 14, 2006, at a Thelonious Monk Institute dinner, sharing the bandstand with Clark Terry. Homefree in 2010 was her seventh and last Concord album; a Christmas record with the Durham-based John Brown Big Band followed in 2012, and then she stopped.

What stopped her was illness at home. Philip Freelon was diagnosed with ALS in 2016, and she and their children cared for him until his death on July 9, 2019. Her sister Debbie died within months of him. The pandemic closed in on the grieving. What came out of it was Time Traveler, recorded in fragments at studios in Pittsboro and Durham between March 2018 and September 2020, released by Origin in 2021 and nominated at the 64th Grammy Awards: a program of songs she and Philip had shared, from a Marvin Gaye medley to "Moon River," built around a self-penned title track. She made AnceStars with her son Pierce Freelon in 2023, a children's record that drew her seventh Grammy nomination, and began a podcast, Great Grief, on the subject she had been living inside. Beneath the Skin, recorded in North Carolina in May and June 2024 and released by Origin in March 2025, is the first album of her career made entirely of her own songs, with Alan Pasqua co-arranging from the piano. Duke University Press published her first book, Beneath the Skin of Sorrow: Improvisations on Loss, that October. In March 2026 she appeared on The Sistering, a collaborative album with the singers Lois Deloatch, Lenora Zenzalai Helm and Kate McGarry, and she was on the bill at the San Jose Jazz Summer Fest in August of that year.

Alongside the singing she has spent thirty-five years on arts education. She founded the Babysong workshops at Duke University Medical Center in 1990, teaching young mothers and health care workers what the human voice does for an infant's brain, and served as national spokesperson for the National Association of Partners in Education. She holds the Eubie Blake Award from the Eubie Blake National Jazz Institute and the Billie Holiday Award from France's Académie du Jazz.

Freelon built her phrasing on horn players rather than on singers, which is audible in the way she moves through a melody: she treats the written line as a starting position and reshapes it, sometimes drastically, rather than ornamenting it at the edges. AllMusic's Thom Jurek describes the instrument itself as a slightly smoky, airy alto, equally at ease in standards, contemporary jazz, soul and gospel, and that range is the point rather than a hedge, since her Concord records move between a Jerome Kern tune, a Laura Nyro song and a spiritual without changing register. The habit of interpretation has divided critics reliably: Christopher Loudon wrote in JazzTimes that Blueprint of a Lady lets a listener see the Billie Holiday songbook from entirely fresh perspectives, while AllMusic's Ken Dryden thought the contemporary settings on the same record strayed far enough from the melodies to sound overblown. Ken Franckling, reviewing it for All About Jazz, put the case for the defense: she pays tribute without imitation, and her phrasing and vocal clarity pull a more positive feeling out of material Holiday sang darkly. Her early influences, by her own account, were Nina Simone and Billy Eckstine plus a set of singers who never recorded, and her teacher was Yusef Lateef, who put her on his own Encounters in 1991, a year before her first album. Since 2018 the subject matter has narrowed and deepened onto loss, and Beneath the Skin is the first record where she wrote all of it herself.