David was a contestant on the 8th season of Dancing with the Stars, partnered with Kym Johnson. By the fourth week of the competition, Grier announced that he had lost 26 pounds. He was eliminated in the fifth week.

Grier got his start on the National Public Radio radio drama adaptation of Star Wars in 1981. He was the voice of a Nameless X-wing fighter pilot during the Battle of Yavin.

Grier was nominated for a Tony Award for Best Featured Actor in a Musical and won the Theatre World Award for The First. He later starred as James "Thunder" Early in the hit Broadway musical Dreamgirls. Grier made his film debut in 1983 in Streamers, directed by Robert Altman. He won the Golden Lion for Best Actor at the Venice Film Festival for the film. He also appeared in the Negro Ensemble Company production A Soldier's Play and reprised his role in the film version A Soldier's Story. Grier also appeared as a geology professor at the fictitious Hillman College in the show A Different World where he was a crush of several of the girls on the show including lead character Denise Huxtable played by Actress Lisa Bonet.

He is also a black belt in taekwondo. Grier was able to showcase his skills in the 1994 film Blankman as his character, Kevin Walker, "The Other Guy," was shown to be particularly adept in martial arts.

In another notable episode - that of September 25, 2002 - Grier stopped by to lament his recent breakup with his girlfriend of four years. He had just found out she had been cheating on him with several famous actors; he coughed while saying the names to avoid legal difficulties. During the show Engineer Anderson slowed down the recording and played it back, and the listeners were able to discern the names Tom Sizemore, Colin Farrell, and Cuba Gooding Jr..

He was often referred to as the third host of the radio show Loveline, as he was a frequent guest and guest host (usually filling in for Adam Carolla). One of his most famous contributions was a bit where he began calling out various pharmaceutical drugs Dr. Drew was recommending to a caller as though they were the names of black children being yelled at by their parents. The episode aired on September 7, 2005, towards the end of the show.

Grier's supposed last appearance on Loveline was April 16, 2006. On his MySpace page, Grier posted:

Grier was married to Maritza Rivera and divorced in 1997. In July 2007, he married Christine Y. Kim, an associate curator of the Los Angeles County Museum of Art. She gave birth to their daughter, Luisa Danbi Grier-Kim on January 10, 2008, at Cedars-Sinai Medical Center, in Los Angeles. On June 9, 2009, according to TMZ, Kim filed for divorce, citing irreconcilable differences.

He is a fan of motorcycles and owns the rare Yamaha YZF-R1 Limited Edition. On the August 10, 2009, episode of Loveline, Grier agreed to auction it to aid Bryan Bishop's Tumor Fund, but walked off set while Carolla and the audio Engineer bickered on air.

Grier made an appearance on the Dave, Shelley, and Chainsaw (DSC) Show (San Diego Jack 100.7 FM) on October 5, 2012 before performances at The Madhouse Comedy Club. He mentioned the "other" David Alan Grier and the "Farrakhan - The Musical" stories.

In May 2013, Grier appeared in Tyler Perry Presents Peeples, playing the role of Virgil Peeples, alongside Kerry Washington and Craig Robinson. Also in 2013, Grier appeared in The Watsons Go To Birmingham, a Hallmark Channel adaptation of Christopher Paul Curtis' 1995 Newbery Honor-winning novel, The Watsons Go to Birmingham – 1963.

He played the Cowardly Lion in NBC's live performance of The Wiz, which aired on December 3, 2015.