She is also the mother of contemporary gospel singer and actress Kierra "Kiki" Sheard, with whom she frequently collaborates.

During the hiatus of the Clark Sisters, Clark-Sheard recorded her debut studio album Finally Karen (1997), which spawned the single, "Balm in Gilead" (a re-recording of a song she originally recorded as part of the Clark Sisters in the 1980s for their Heart & Soul album) the R&B-tinged singles "Just for Me" and "Nothing Without You" (with Faith Evans).

[2] Clark-Sheard then was hospitalized in 2001 after a blood vessel burst during a bariatric surgery, resulting in doctors giving her a 2% chance of survival.

The youngest of six children, Clark-Sheard's siblings are Leo, Jacky, Denise, Elbernita "Twinkie" and Dorinda.

The 2003 follow-up The Heavens Are Telling (exactly six years after her heralded debut album Finally Karen) came when Elektra Records was being dissolved into Atlantic Records, and failed to match the commercial success of Clark-Sheard's previous albums, peaking 106 places below 2nd Chance at #188 on the U.S.

[8] In 2005, after a bidding war with several labels, Clark-Sheard signed with Word Records and issued It's Not Over (originally titled Finally Karen Returns), the sequel to her 1997 debut album Finally Karen was set to be released November 15, 2005, Clark-Sheard's 45th birthday, but was delayed and released the following year.

It was Clark-Sheard's first solo album not to feature guest vocals from her daughter (Kierra Sheard) and was the first to include production from Israel Houghton – who handled the majority of the project.

[8][9] As the songwriter, on February 10, 2008, Clark-Sheard won the Grammy Award for Best Gospel Song for "Blessed & Highly Favored" sung by the Clark Sisters.

On January 31, 2010, Clark-Sheard won the Grammy Award for Best Gospel Performance for Wait on the Lord which she was featured with Donnie McClurkin.

Drew Sheard II, sister Dorinda Clark Cole, niece Angel Chisholm and cousin J. Moss.

Clark-Sheard released her latest single "Sunday A.M" in 2014, which was nominated for the Best Gospel Song in the 57th Annual Grammy Awards.

In 2019, Clark-Sheard was in talks to play Kitty Parham, a member of the Famous Ward Singers in Aretha Franklin's biopic Respect.

[10] Karen was portrayed by her daughter, Kierra Sheard in the Lifetime TV biopic The Clark Sisters: First Ladies of Gospel, released April 11, 2020.

Clark-Sheard serves as the First Lady of Greater Emmanuel Institutional Church of God in Christ in Detroit, where her husband is senior pastor.

[12] In 2001, Clark-Sheard was faced with a life-threatening crisis when a blood vessel burst during a scheduled bariatric surgery.