De Luca was born and raised in Brooklyn, New York. His mother was a German-Jewish immigrant, and his father, who was Italian American and Catholic, worked at ConEdison.[1][2] De Luca began pursuing a career in show business in 1986. Originally tapped to work as a story editor, he rose fairly quickly through the ranks, thanks in part to his mentor, chairman and co-founder of New Line Cinema Robert Shaye. De Luca completed his degree from Tisch School of the Arts of New York University in 1995.[3]
After New Line Cinema, De Luca became President of Production at DreamWorks, his tenure lasting from 2001 to 2004.
After his contract with DreamWorks ended, De Luca signed a production deal with Sony Pictures and started his own production company, Michael De Luca Productions. His first release under his production company was Ghost Rider (2007) starring Nicolas Cage, followed by 21 and The Love Guru (both 2008) starring Mike Myers.
On January 3, 2020, it was announced that De Luca had been appointed Chairman of the MGM Motion Picture Group.[7] In July 2022 he and Pamela Abdy left for Warner Bros. Pictures Group, taking up the roles of co-chairpersons and CEO, respectively.[8]
In 2009, he married actress Angelique Madrid (born 1974) from Ft. Worth, Texas, who was a contestant on the first season of ABC's The Bachelor. They have two children.[2]