Woodard's notable films include Grand Canyon (1991), Passion Fish (1992), Heart and Souls (1993), Crooklyn (1994), How to Make an American Quilt (1995), Primal Fear (1996), Star Trek: First Contact (1996), Down in the Delta (1998), 12 Years a Slave (2013), and Juanita (2019).

In the Marvel Cinematic Universe (MCU) she portrayed the "Black" Mariah Stokes Dillard in the Netflix series Luke Cage (2016–2018).

[11] She later appeared in the NBC miniseries The Sophisticated Gents, and had a regular role alongside Catherine Hicks and Tim Matheson in the short-lived comedy-drama Tucker's Witch (1982–83).

She was nominated for Primetime Emmy Awards for her roles in the films Words by Heart (1985), Unnatural Causes (1986), and A Mother's Courage: The Mary Thomas Story (1989).

[12] In 1986, Woodard starred opposite Farrah Fawcett in the drama film Extremities, which was based on the 1982 Off-Broadway play by William Mastrosimone.

[15][16] The next year, Woodard received major critical acclaim for her performance opposite Mary McDonnell in the drama film Passion Fish, written and directed by John Sayles.

The film depicts the struggles of a recently paralyzed daytime soap opera star, and how her outlook is influenced by her nurse, Chantelle, a recovering drug addict played by Woodard.

[20] In that same year, she had a comedic role in the fantasy film Heart and Souls opposite Robert Downey, Jr., for which she was nominated for a Saturn Award for Best Supporting Actress.

In 1998, she starred as an alcoholic single mother from Chicago forced to spend a summer with her uncle in Mississippi, in the critically acclaimed independent drama Down in the Delta directed by Maya Angelou, her How to Make an American Quilt co-star.

In 1999, Woodard had roles in two films: Mumford (alongside her Passion Fish co-star Mary McDonnell), and The Wishing Tree as lead character.

[12] In next year, she received a Primetime Emmy nomination for her performance as the Queen in the critically acclaimed Hallmark miniseries Gulliver's Travels, based on the classic Jonathan Swift novel.

Her performance as the title character in the latter film, as a nurse who consoled many of the subjects of the notorious 1930s Tuskegee study of untreated Blacks with syphilis, earned widespread critical acclaim,[26][27][28][29] sweeping all television awards in the Outstanding Lead Actress in a Miniseries or Movie category, including Primetime Emmy (besting nominees Meryl Streep, Helen Mirren, Glenn Close, and Stockard Channing), Golden Globe, Satellite, NAACP, CableACE, and Screen Actors Guild Awards.

[35] Woodard's portrayal of Betty was praised and resulted in a nomination for the Primetime Emmy Award for Outstanding Supporting Actress in a Comedy Series in 2006.

In a review of the second-season premiere, Michael Slezak of Entertainment Weekly thought that the Applewhite mystery would help reduce the show's chances of falling into a sophomore slump.

[38] She left the series in the second-season finale episode.Woodard was nominated for Primetime Emmys for her roles in the television films The Water Is Wide and Pictures of Hollis Woods (2007).

[39] Los Angeles Times critic Bob Baker said in his review: "The film takes off when Woodard's and Kathy Bates' characters go on a Thelma & Louise-style road trip.

[41] In next year, she appeared in the independent drama American Violet, playing the mother of a 24-year-old African-American woman wrongfully swept up in a drug raid.

From 2010 to 2011, Woodard starred as Lt. Tanya Rice in the TNT comedy-drama series Memphis Beat, winning a Gracie Allen Award for each of its two seasons.

One critic said: "I originally tuned in for Jason Lee, who plays a police detective named Dwight who likes to croon the blues.

[47][48] Also in 2012, Woodard appeared in the Lifetime television remake of the 1989 comedy-drama film Steel Magnolias as Ouiser, a role previously played by Shirley MacLaine.

[54] In 2013, Woodard appeared in Steve McQueen's historical drama film 12 Years a Slave as Mistress Harriet Shaw, a formerly enslaved woman who has risen in the Southern caste system.

[74][75] She had a small role in Marvel's film Captain America: Civil War (2016), playing Miriam Sharpe, the mother of an American citizen killed in the battle of Sokovia.

[79][80] Woodard played the title character in Juanita (2019), an independent drama based on Sheila Williams' book Dancing on the Edge of the Roof.

The film centers on a prison warden (Woodard) who confronts her own psychological demons as she develops an emotional connection to the death row inmate (played by Aldis Hodge) she is scheduled to execute.

Samantha Bergeson from IndieWire wrote in her review: "Alfre Woodard, too good for this film, graces us onscreen as a kind pediatrician who treats Alex because he acts like a little kid.

"[99] Woodard executive produced and co-starred in the CBC Television period drama miniseries The Porter, which premiered in 2022 to positive reviews and became the most nominated show at the 11th Canadian Screen Awards.

Woodard next appeared in the 2024 film adaptation of 'Salem's Lot playing the role of Dr. Cody,[102] and set to star alongside Morgan Freeman in Hate To See You Go.

[113] In February 2009, she joined a group of American film directors and actors on a cultural trip to Iran at the invitation of the "House of Cinema" forum in Tehran.

Historians helped Woodard locate evidence that Alex was assessed a poll tax in 1867, indicating that he was registered to vote two years after the Civil War ended.

On April 15, 1898, Alex Woodard and his wife Elizabeth sold their 80 acres to her brother, Aaron Stell, as they had moved to Wharton County, Texas, by that time.