Michele has appeared in music videos by R&B singers Freddie Jackson and Eric Gable. In 1989 she sued actor Eddie Murphy in a high-profile Hollywood lawsuit alleging she was fired from the movie Harlem Nights for rejecting his romantic advances. "She had the role that's now being played by Jasmine Guy, from A Different World," Murphy told Rolling Stone. "The fact of the matter is, I wanted someone with greater marquee value than Michael Michele. She wasn't working out. As for her claim that I was touching her, realistically speaking, if you're gonna be a sleaze and try to sleep with somebody, you try to sleep with 'em before you give 'em the part… In her lawsuit, she says I tried to touch her, like I was a pervert. I never tried to touch this woman. We had, like, four conversations, each time with up to sixty people around us on a sound stage. But the lawsuit itself didn't bother me. Lawsuits for me are an occupational hazard." Michele's suit was later settled out of court for an undisclosed sum.
In 1991, Michele had a starring role opposite Wesley Snipes in the 1991 film New Jack City directed by Mario Van Peebles. Despite the film's success, Michele did not have her next movie role until six years later, starring opposite Marlon Wayans in the comedy film The 6th Man. In 1992, she went on to star on the CBS late-night crime drama series Dangerous Curves, which ran for two seasons. In 1993, she played a leading role in the six-part NBC soap opera miniseries Trade Winds. The following year, she had a major recurring role in the Fox police drama series New York Undercover. She left the show in early 1995 to play one of the leads in the CBS prime time soap opera Central Park West alongside Mädchen Amick, Lauren Hutton and Raquel Welch. The series was not successful and was cancelled after two seasons in 1996.
In 1998, Michele joined the cast of NBC police drama Homicide: Life on the Street as Det. Rene Sheppard on the show's final season. She received her first NAACP Image Award for Outstanding Actress in a Drama Series nomination for this role. Michelle reprised her role in a Law & Order episode in 1999 and in the television movie Homicide: The Movie in 2000. She later joined another NBC series, medical drama ER playing Dr. Cleo Finch from 1999 to 2002, for three seasons. She received another NAACP Image Award nomination.
In 2001, Michele played Veronica Porché Ali in the biographical drama film Ali opposite Will Smith. She later had two more movie roles: crime drama Dark Blue (2002) and romantic comedy How to Lose a Guy in 10 Days (2003). She returned to television in 2004, with a starring role in the short-lived UPN legal drama series Kevin Hill opposite Taye Diggs. In 2007, she guest starred on Law & Order: Special Victims Unit and in two episodes of House as a doctor who had previously worked with the CIA. In 2009 Michele starred in the Hallmark Channel film Relative Stranger with fellow ER cast member Eriq La Salle. In 2011, Michele had a recurring role on the CW teen drama Gossip Girl. In the late 2000s and early 2010s, Michele also starred in a number of unsold television pilots.
In 2017, Michele returned to series regular work playing villainous Ayanna Floyd, president of the record label, in the Fox prime time soap opera Star. Her character was described as a modern-day black Alexis Carrington. She also was cast in a recurring role in the Oprah Winfrey Network drama series Queen Sugar.
|1990||Def by Temptation||Lady #6||Film debut|
|1991||New Jack City||Selina|
|1997||The 6th Man||R.C. St. John|
|1998||The Substitute 2: School's Out||Kara Lavelle||Straight-to-DVD|
|2001||Ali||Veronica Porché Ali|
|2002||Dark Blue||Beth Williamson||Nominated—Black Reel Award for Best Supporting Actress|
|2003||How to Lose a Guy in 10 Days||Judy Spears||Nominated—Teen Choice Award for Choice Movie Villain|
|1988||1st & Ten||Gillian||Episode: "Saturday, Bloody Saturday"|
|1991||Private Times||Failed TV pilot|
|1992–1993||Dangerous Curves||Holly Williams||Series regular, 34 episodes|
|1993||Trade Winds||Maxine Phillips||Miniseries|
|1994–1995||New York Undercover||Sandra Gil||Recurring role (season 1), 12 episodes|
|1995–1996||Central Park West||Nikki Sheridan||Series regular, 21 episodes|
|1998||Peter Benchley's Creature||Tauna||Miniseries|
|1998–1999||Homicide: Life on the Street||Detective Rene Sheppard||Main role (season 7), 22 episodes|
Nominated — NAACP Image Award for Outstanding Actress in a Drama Series
|1999||Law & Order||Det. Rene Sheppard||Episode: "Sideshow"|
|1999–2002||ER||Dr. Cleo Finch||Series regular (seasons 6–8), 55 episodes|
Nominated — NAACP Image Award for Outstanding Supporting Actress in a Drama Series (2001)
Nominated — Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Drama Series (2000-2001)
|2000||Homicide: The Movie||Detective Rene Sheppard||Television film|
|2004–2005||Kevin Hill||Jessie Gray||Main role, 22 episodes|
|2005||The Hunt for the BTK Killer||Detective Baines||Television film|
|2006||Company Town||Bridget Wilson||Television pilot|
|2007||Law & Order: Special Victims Unit||Valerie Sennet||Episode: "Burned"|
|2007||House||Dr. Samira Terzi||Episodes: "Whatever It Takes", "Ugly"|
|2007||Judy's Got a Gun||Pamela Coates||Television pilot|
|2009||Relative Stranger||Charlotte||Television film|
|2011||Eden||Tara Martin||Television pilot|
|2011||Gossip Girl||Jane||Recurring role, 4 episodes|
|2014||Delirium||Elyse Hargrove||Television pilot|
|2015||The Following||Sheila||Episode: "A Hostile Witness"|
|2016||Blue Bloods||Lois Potter||Episode: "Unbearable Loss"|
|2017–2018||Star||Ayanna Floyd||Series regular, 18 episodes|
|2017–2018||Queen Sugar||Darlene Sutton||Recurring role, 4 episodes|
|2019–present||Dynasty||Dominique Deveraux||Recurring role (season 2); Series Regular (Season 3-Present)|
|Dynasty: Season 2 (3/22)|
|"Twenty-Three Skidoo":||"Ship of Vipers":||"The Butler Did It":||"Snowflakes in Hell":||"Queen of Cups":||"That Witch":||"A Temporary Infestation":||"A Real Instinct for the Jugular":||"Crazy Lady":||"A Champagne Mood":||"The Sight of You":|
|"Filthy Games":||"Even Worms Can Procreate":||"Parisian Legend Has It...:||"Motherly Overprotectiveness":||"Miserably Ungrateful Men":||"How Two-Faced Can You Get":||"Life is A Masquerade Party":||"This Illness of Mine":||"New Lady in Town":||"Thicker Than Money":||"Deception, Jealousy, and Lies":|
|Dynasty: Season 3 (14/20)|
|"Guilt Trip to Alaska":||"Caution Never Won A War":||"Wild Ghost Chase":||"Something Desperate":||"Mother? I’m At La Mirage":||"A Used Up Memory":||"Shoot From the Hip":||"The Sensational Blake Carrington Trial":||"The Caviar, I Trust, Is Not Burned":||"What Sorrows Are You Drowning?":|
|"A Wound That May Never Heal":||"Battle Lines":||"You See Most Things in Terms of Black & White":||"That Wicked Stepmother":||"Up A Tree":||"Is The Next Surgery on The House?":||"She Cancelled...":||"You Make Being a Priest Sound Like Something Bad":||"Robin Hood Rescues":||"My Hangover's Arrived":|
- Michele's favourite food is Pizza and Caviar.
- Michele's favourite colours are yellow, and white.