Headley was born in Trinidad, the daughter of Hannah and Eric Headley. In 1989, she moved to Fort Wayne, Indiana in the United States at the age of fifteen with her mother and brother Eric Junior when her father was offered a job as pastor of McKee Street Church of God with headquarters in Anderson, Indiana. Headley attended Northrop High School, and was a member of their resident show choir, Charisma, and starred as Fanny Brice in the school's production of Funny Girl. After graduating from Northrop High School, Headley attended Northwestern University from 1993 to 1996, to study communications and musical theatre until the last day of her junior year, when she made the decision to become a part of the musical Ragtime and drop out of school. In 2003, Headley married Brian Musso, an investment advisor who briefly played for the New York Jets. Both attended Northwestern University. On December 1, 2009, they welcomed their first child John David. Headley had her second son Jordan Chase August 18, 2014. In April 2019, the couple welcomed a third child, a daughter. Headley regularly performs with Vertical Church Band, the worship team from Harvest Bible Chapel. She is featured in their song "How Great Is The Love" and "All Glory".
Headley released her debut album, This Is Who I Am, in October 2002 with RCA Records. Although its first single, "He Is", was not very successful, the second single, "I Wish I Wasn't", achieved moderate success. The work on this album earned her a Grammy Award nomination for Best Female R&B Vocal Performance and for Best New Artist making her the first Tony Award winner to be nominated for this award. Her second album, In My Mind was delayed due to the various executive shake-ups associated with RCA parent BMG's merger with Sony. Under BMG North America chairman/CEO Clive Davisfor the first time, Headley released her second album In My Mind in January 2006. The title track "In My Mind" was released as the first single; and its music video was directed by Diane Martel. The song reached number-one on the U.S. Hot Dance Music/Club Play chart. The second single "Me Time" was sent to Urban AC radio only. An album track, "Am I Worth It", served to promote Headley's New March of Dimes Educational Campaign "I Want My 9 Months". In 2009, Headley, along with Al Green, released a version of the song "People Get Ready" on the compilation album . In January 2010 she won her first Grammy Award for Best Contemporary R&B Gospel Album for Audience of One on the EMI Gospel label. In December 2010, Headley performed a duet version of "Blue Christmas" and "My Prayer" with Italian tenor Andrea Bocelli on his "My Christmas" tour in 5 US cities. At the Prudential Center in Newark, NJ, on December 4, 2010, the audience insisted on a second encore with Bocelli. Bocelli had to summon the detail to go and bring her back on stage. Headley released her album Only One in the World on September 25, 2012, with the lead single "A Little While". In September 2013, Headley appeared on America's Got Talent with Il Divo and sang "Can You Feel the Love Tonight?" from The Lion King. She also appeared with Il Divo on Broadway for a limited concert run in 2013.
Acting
In 2017, Headley began appearing in recurring roles on the TV series She's Gotta Have It. The following year, she began appearing as Gwen Garrett in a recurring role on the TV series Chicago Med. In 2019, Headley was cast as one of the three leads in the Netflix series Sweet Magnolias.
