The fiercely creative Elfman got his start in the 1970s playing in two theater troupes started by his older brother Richard - Le Grande Magic Circus, and then The Mystic Knights of the Oingo Boingo. After eight years in the Mystic Knights as a singer, composer, guitarist, and trombonist, Danny Elfman pared the troupe down to a rock band, just as Richard Elfman was making Forbidden Zone, which captured the group in the middle of its transformation to Oingo Boingo. Elfman's vocal range and manic stage presence led Oingo Boingo to a long series of recordings and a strong cult following.

Building on his experience scoring music for theater and independent film, Elfman's career took another big step when he composed the soundtrack for Pee-wee's Big Adventure, his first big budget project. This also began his long association with the film director Tim Burton, as Danny Elfman has scored all but one of his films, including Beetlejuice, Batman, Batman Returns, Edward Scissorhands, Sleepy Hollow, Mars Attacks!, Big Fish, Charlie and the Chocolate Factory, The Nightmare Before Christmas and Corpse Bride. Elfman's musical signature in these films helps create the fantasy and gothic style typical of Burton's films, using instrumentation such as the pipe organ and boys chorus.

As a film composer, Elfman is recognizably influenced by Nino Rota, Bernard Herrmann, and Carl Stalling. His scores heavily utilize the 3/4 time signature, making many of his more memorable themes sound like gothic waltzes.

In The Nightmare Before Christmas, Elfman contributed the singing voice of the main character, Jack Skellington, as well as writing the lyrics and composing the songs and score. Elfman also provided all of the singing voices for the Oompa Loompas played by Deep Roy in Charlie and the Chocolate Factory. In Corpse Bride, Danny Elfman sang the voice of Bonejangles in songs as well.

He has also scored many other films including The Frighteners, Back to School, Chicago, Dick Tracy, Freeway, Good Will Hunting, Hulk, Midnight Run, both movies in the Men in Black series, Mission: Impossible, The Family Man, and Sam Raimi's Darkman, Army of Darkness, Nightbreed, A Simple Plan, Spider-Man and Spider-Man 2.

Elfman has also composed theme music for several television series, including The Simpsons, Batman: The Animated Series, The Flash, Sledge Hammer!, Tales from the Crypt, Dilbert, and the opening theme for Desperate Housewives, as well as the Xbox console game Fable. The song "This is Halloween" from Tim Burton's "The Nightmare Before Christmas" also appeared in Kingdom Hearts. His songs in the movie have been remixed by different artists for The Nightmare Before Christmas: Oogie's Revenge.

On November 29, 2003, Elfman married Bridget Fonda. They have one son, Oliver, born in January, 2005. He is a fan and friend of the band Primus. Danny's nephew Bodhi Elfman is married to Dharma and Greg star Jenna Elfman.

His mother, Blossom Elfman, wrote young adult novels in the seventies. One was made into a TV movie called The Girls of Huntington House which starred Shirley Jones and a young Sissy Spacek.