Nash received two Primetime Emmy Awards nominations for starring as Denise "Didi" Ortley in the comedy-drama series Getting On (2013–2015).

She has also portrayed Lolli Ballentine in the sitcom The Soul Man (2012–2016), and Denise Hemphill in the horror-comedy series Scream Queens (2015–2016).

Nash collaborated with director Ava DuVernay in the drama films Selma (2014) and Origin (2023), and the miniseries When They See Us (2019), for which she was nominated for another Primetime Emmy Award.

[4] Nash made her professional acting debut in the 1995 comedy-drama film, Boys on the Side starring Whoopi Goldberg.

[4] On television, she later guest-starred in NYPD Blue, Judging Amy, Reba, Girlfriends, CSI: Crime Scene Investigation, and ER.

She also appeared in the 1999 comedy film Cookie's Fortune directed by Robert Altman, and had a recurring role on the CBS drama series City of Angels in 2000.

She hosted Clean House on the Style Network from 2003 to 2010, as well as providing the voice of Mrs. Boots on the ABC Family animated series Slacker Cats, and starred as Rhonda, opposite Jerry O'Connell, in the short-lived Fox sitcom Do Not Disturb in 2008.

[6] Nash appeared on the tenth season of ABC's Dancing with the Stars beginning in March 2010, where she was partnered with Louis van Amstel.

[citation needed] In 2012, Nash began starring opposite Cedric the Entertainer in the TV Land sitcom The Soul Man, a spinoff of Hot in Cleveland.

[19] Also that year, Nash joined the cast of the Fox comedy series The Mindy Project in a recurring role as Dr. Jean Fishman, a rival of the title character.

[20][21] From 2015 to 2016, Nash co-starred on the Fox horror-comedy series Scream Queens[2] as a security guard, and then FBI Agent Denise Hemphill.

[25] In 2017, Nash was cast in a leading role in the TNT crime comedy-drama series Claws, produced by Rashida Jones, about a South Florida nail salon.

[35] For her performance, she received critical praise and a nomination for Primetime Emmy Award for Outstanding Lead Actress in a Limited Series or Movie.

She starred in the Lifetime movie Stolen by My Mother: The Kamiyah Mobley Story playing Gloria Williams, her abductor.

[44] Nash guest-starred on two episodes of The Rookie, titled "Simone" and "Enervo", which served as a backdoor pilot centered on her character and aired on April 24 and May 1, 2022.

[51] The following year, she starred in the biographical drama film Origin by Ava DuVernay, based on the life of Isabel Wilkerson.

It premiered at the 80th Venice International Film Festival on September 6, 2023, and began a limited theatrical release in January 2024.

[52][53] In February 1993, Nash's brother Michael Ensley was shot and killed at the age of 17 by a 16-year-old gunman at Reseda High School in California.

She said in an appearance on The Ellen DeGeneres Show that she did not feel that she was "coming out" as she was not sexually repressed prior to her marriage to Betts.