She has appeared in numerous films, including Men of Honor (2000), Undercover Brother (2002), Ray (2004), Freedomland (2006), The Taking of Pelham 123 (2009), The Help (2011), The Birth of a Nation (2016), and If Beale Street Could Talk (2018).

For her portrayal of Oracene Price in the sports drama King Richard (2021), she was nominated for the Academy Award for Best Supporting Actress.

[6] In 1995, Ellis made her professional acting debut appearing as Ariel opposite Patrick Stewart's Prospero in a Broadway revival of William Shakespeare's The Tempest.

From 1996 to 1997, Ellis starred as Officer Leslie Joyner in the ABC police drama series High Incident, created by Steven Spielberg.

The following year, she played daughter of Samuel L. Jackson's character in the mystery-drama film The Caveman's Valentine, directed by Kasi Lemmons and based on George Dawes Green's 1994 novel of the same name.

In 2009, she co-starred alongside Cuba Gooding Jr. and Kimberly Elise in the made-for-television film, Gifted Hands: The Ben Carson Story.

In 2014, she played Vicki Anderson in the biographical drama film Get On Up about the life of singer James Brown, which was also directed by Tate Taylor.

As lead actress, Ellis starred in the independent films Money Matters (2011), The Volunteer (2013), Romeo and Juliet in Harlem (2014), and Una Vida: A Fable of Music and the Mind (2014).

She also played Ashley Judd's best friend in the 2012 ABC miniseries Missing, and had another role on the CBS procedural, NCIS: Los Angeles.

[22][23] In 2014, Ellis was cast as the lead in the international co-production epic miniseries The Book of Negroes, based on Lawrence Hill’s bestselling 2007 novel.

"Except for the first installment that focuses on Aminata’s girlhood, Ellis is present in nearly every scene, aging decades and displaying a stunning range of emotion.

[33] In 2016, Ellis co-starred in the historical drama film The Birth of a Nation, based on the story of the 1831 slave rebellion led by Nat Turner.

[36] Also in 2016, she was cast opposite Keke Palmer in the drama film Pimp about life for women on the streets of New York and work in the illegal sex trade.

[44][45] She received NAACP Image Award for Outstanding Actress in a Television Movie, Mini-Series or Dramatic Special nomination for her performance.

In 2024, Ellis starred alongside Uzo Aduba and Sanaa Lathan in The Supremes at Earl's All-You-Can-Eat, an adaptation of Edward Kelsey Moore's 2013 novel of the same name.

Ellis then starred alongside Andra Day, Glenn Close and Mo'Nique in Netflix's exorcism horror-thriller film The Deliverance, directed by Lee Daniels.

[66] Ellis starred opposite André Holland and Andra Day in the Sundance-premiered drama film Exhibiting Forgiveness, directed by Titus Kaphar and released on October 18, 2024.

[67] She co-starred with Hamish Linklater and Fred Hechinger in the period drama film Nickel Boys, an adaptation of the 2019 novel by American novelist Colson Whitehead, released in December 2024.