Born and raised in Toronto, she began performing on television commercials at age 12, and entered various talent shows in her teenage years before becoming a professional backing vocalist for Celine Dion.

After receiving many rejection letters from Canadian record labels that claimed their "quota" had been reached, Cox moved to Los Angeles in 1994 with producer and songwriting partner, Lascelles Stephens.

Featuring production from Dallas Austin, Keith Crouch, Tim & Bob, and Kenneth "Babyface" Edmonds, she released her self-titled debut album the same year.

A middling commercial and critical success, the album peaked at number 102 on US Billboard 200 but emerged as a steady seller, eventually receiving a gold certification by the Recording Industry Association of America (RIAA), while going platinum in Canada.

As with her self-titled debut album, her sophomore effort was once again executive-produced by Davis, but featured more uptempo, contemporary R&B, and a slew of new producers and personnel to incorporate dance and club music, including Montell Jordan, Anthony "Shep" Crawford, Rodney "Darkchild" Jerkins, and DJ Quik.

In 2000, Cox made her acting debut when she starred in Clement Virgo's Canadian drama film Love Come Down, playing a nightclub singer.

[11] In February 2004, Cox made her Broadway debut in the Elton John-Tim Rice musical Aida when she replaced singer Michelle Williams in her role of the Nubian princess.

To sustain demand for Cox's club appearances, while focused on her family and new album projects, she released a dance single titled "House Is Not a Home" on Nervous Records in January 2006.

The same year, Cox co-starred alongside Golden Brooks and Darius McCrary in Leslie Small's film A Good Man is Hard to Find.

Based on the musical stage play of the same name, the comedy depicts the story of three women who each undergo romantic crises that challenge their personal and spiritual relationships.

[16] She also contributed the song "This Gift" to the soundtrack of the 2008 romantic drama film Meet the Browns, directed by Tyler Perry, and served as a supporting act on Cyndi Lauper's True Colors Tour 2008.

In support of the album, Cox joined forces with American R&B singer Kenny Lattimore for the joint Timeless Promise Tour in July 2009.

[20] Also in 2009, she was featured on the single "Leave the World Behind", a house track produced by four DJs Axwell, Steve Angello, Sebastian Ingrosso and Laidback Luke.

[22] While the trio recorded several tracks together, their joint album The Queen Project eventually failed to materialize due timing issues and label politics.

[25] In September 2012, Cox gave her inaugural performance as the female lead Lucy in a revival of the musical Jekyll & Hyde which toured North America for twenty-five weeks.

[36] In February 2020, Cox starred opposite Roger Guenveur Smith in the BET+ television thriller Influence, an adaption of Carl Weber's same-titled 2018 novel, portraying a big-name celebrity singer accused of killing her husband.

[35] Also in 2020, she appeared as a guest host in an episode of Canada's Drag Race and started a webseries titled COXtales with Deborah Cox during the global COVID-19 pandemic.

"[38] In 2021, Cox was added to the BET series First Wives Club during its second season, playing the role of musician Regina alongside Michelle Buteau and Jill Scott.

[39] The same year, she co-starred as Wendy in the HBO Max post-apocalyptic dystopian fiction miniseries Station Eleven,[40] and appeared on "Summe of Love," another collaboration with Israeli producer Offer Nissim.