Harris began his career as a child actor and was discovered by playwright Mark Medoff at a drama camp in Las Cruces, New Mexico.
Medoff later cast him in the 1988 drama film Clara's Heart, starring Whoopi Goldberg and based on the novel of the same name by Joseph Olshan.
Clara's Heart earned Harris a Golden Globe nomination.
The same year, he starred in Purple People Eater, a children's fantasy.

Harris' first film role as an adult was 1995's Animal Room, although he portrayed a teenager.
His subsequent film work has included supporting roles in The Next Best Thing, Undercover Brother, and Starship Troopers.
Harris plays a fictionalized, hyper-womanising, lewd version of himself in the Harold and Kumar stoner comedy films Harold & Kumar Go to White Castle, Harold & Kumar Escape from Guantanamo Bay, and A Very Harold & Kumar 3D Christmas.

In 2010, Harris provided voice acting for the role of the adult Dick Grayson (Nightwing) in the animated film Batman: Under the Red Hood and the beagle Lou in the film Cats & Dogs: The Revenge of Kitty Galore.
The same year, he played the lead in the indie comedy The Best and the Brightest.
On March 7, 2010, he made a surprise appearance at the 82nd Academy Awards, delivering the opening musical number.
He starred in the films The Smurfs (2011) and The Smurfs 2 (2013).
Harris provided the voice of Steve the Monkey in the Cloudy with a Chance of Meatballs film franchise.

In 2014, Harris showed a more serious side in Gone Girl, directed by David Fincher.
Harris co-starred in the film as Desi Collings, the wealthy and obsessed ex-boyfriend of Amy Dunne, played by Rosamund Pike.
Harris has said: "I was pinching myself at the opportunity" to work with Fincher, he received general praise from critics for his performance, as did the film.

On February 22, 2015, Harris hosted the 87th Academy Awards; it was his first time hosting the ceremony, and the first time an openly gay man hosted the Academy Awards.

In October 2019 it was announced Harris would star in the fourth installment of The Matrix franchise.
Harris began his career as a child actor and was discovered by playwright Mark Medoff at a drama camp in Las Cruces, New Mexico. Medoff later cast him in the 1988 drama film Clara's Heart, starring Whoopi Goldberg and based on the novel of the same name by Joseph Olshan. Clara's Heart earned Harris a Golden Globe nomination. The same year, he starred in Purple People Eater, a children's fantasy.
Harris' first film role as an adult was 1995's Animal Room, although he portrayed a teenager. His subsequent film work has included supporting roles in The Next Best Thing, Undercover Brother, and Starship Troopers. Harris plays a fictionalized, hyper-womanising, lewd version of himself in the Harold and Kumar stoner comedy films Harold & Kumar Go to White Castle, Harold & Kumar Escape from Guantanamo Bay, and A Very Harold & Kumar 3D Christmas.
In 2010, Harris provided voice acting for the role of the adult Dick Grayson (Nightwing) in the animated film Batman: Under the Red Hood and the beagle Lou in the film Cats & Dogs: The Revenge of Kitty Galore. The same year, he played the lead in the indie comedy The Best and the Brightest. On March 7, 2010, he made a surprise appearance at the 82nd Academy Awards, delivering the opening musical number. He starred in the films The Smurfs (2011) and The Smurfs 2 (2013). Harris provided the voice of Steve the Monkey in the Cloudy with a Chance of Meatballs film franchise.
In 2014, Harris showed a more serious side in Gone Girl, directed by David Fincher. Harris co-starred in the film as Desi Collings, the wealthy and obsessed ex-boyfriend of Amy Dunne, played by Rosamund Pike. Harris has said: "I was pinching myself at the opportunity" to work with Fincher, he received general praise from critics for his performance, as did the film.
On February 22, 2015, Harris hosted the 87th Academy Awards; it was his first time hosting the ceremony, and the first time an openly gay man hosted the Academy Awards.
In October 2019 it was announced Harris would star in the fourth installment of The Matrix franchise.
Neil Patrick Harris