Ellis was born in Harvey, Illinois, near Chicago. When Ellis and his siblings were younger, their mother, a single parent after her divorce from her husband, broke down over the death of her brother. Ellis and his siblings became wards of the state as a result. They were then raised in Bessemer, Alabama, by their grandmother. In Alabama, Ellis attended Jess Lanier High School for a year, then transferred to McAdory High School. He moved back to Illinois at age 15, where he lived with his maternal aunt, and in 1997 he graduated from Thornridge High School in Dolton, Illinois.
He joined the United States Marines at the age of 17, but quit not long afterwards. Following this, Ellis attended Illinois State University.
In 2000, at the age of 22, he was accepted for enrollment at Juilliard, where he befriended True Blood colleague Rutina Wesley. Ellis later earned a Bachelor of Fine Arts degree from Juilliard in 2004.
In 2007, Ellis was cast as Lafayette Reynolds in the pilot for True Blood, as a short order cook at Merlotte's, a drug dealer, a member of Jason Stackhouse's road crew, and Tara Thornton's cousin. The pilot was shot in the early summer of 2007 and was officially ordered to series in August. Production on the series began later that fall.
In casting, Alan Ball had concerns that the character's homosexuality would be a dominating trait, "because you don't want to bring in someone who's going to play that in a phony way". Nelsan Ellis says that it took him a few episodes to find the character. Ellis says that he based many of Lafayette's mannerisms on his mother and his sister, and that the costuming also helped him to get into character. He told The Philadelphia Inquirer:
I have more makeup on than any of the females in the cast. Once they get me with the fake eyelashes and the eye makeup, I listen to some Rihanna and I'm there.
The series premiered on September 7, 2008, and concluded on August 24, 2014, comprising seven seasons and 80 episodes. In 2008, Ellis received a Satellite Award from the International Press Academy for best supporting actor in a television series for his role as Lafayette Reynolds. In 2009, he was nominated for a Scream Award for "Best Supporting Actor" for True Blood.
In 2012, Ellis was cast as Martin Luther King, Jr. in a supporting performance in Lee Daniels' The Butler. The Butler received mostly positive reviews from critics, with a 71% rating on the film critic aggregate site Rotten Tomatoes, based on 171 reviews.
On October 21, 2013, Ellis joined the cast of Get on Up, a biographical drama film about the life of singer James Brown. He portrayed Bobby Byrd, Brown's long-time friend. Get on Up was met with positive reviews from critics. In 2014, the film had a rating of 80% on the review aggregator site Rotten Tomatoes, based on 150 reviews, with an average rating of 6.8/10.
Ellis died at the age of 39 on July 8, 2017, in Woodhull Medical Center, New York, after complications from heart failure. His family released a statement on July 10 saying that Ellis had been trying to quit drinking alcohol in the days before his death, and that alcohol withdrawal syndrome led to his heart failure.While at Juilliard, Ellis wrote a semi-autobiographical play entitled Ugly, which was performed at the school and later won the Lincoln Center's Martin E. Segal Award. The play was influenced by his pregnant sister's murder at the hands of her husband.2008 – Satellite Award from the International Press Academy for best supporting actor in a television series for his role as Lafayette Reynolds in HBO's True Blood.2009 – NewNowNext Awards "Brink of Fame: Actor" award.2009 – Ewwy Award for "Best Supporting Actor in a Drama Series" for True Blood.2009 – Scream Award for "Best Supporting Actor" for True Blood.2011 – NAACP Image Award for "Outstanding Supporting Actor in a Drama Series" for True Blood.