Price was a lifelong smoker. He had long suffered from emphysema and Parkinson's disease, which had forced his role in Edward Scissorhands to be much smaller than intended.

His illness also contributed to his retirement from Mystery, as his condition was becoming noticeable on-screen. He died of lung cancer on October 25, 1993. He was cremated and his ashes scattered off Point Dume in Malibu, California.

The A&E Network aired an episode of Biography highlighting Price's horror career the next night, but because of its failure to clear copyrights, the show was never aired again. Four years later, A&E produced its updated episode, a show titled Vincent Price: The Versatile Villain, which aired on October 12, 1997. The script was by Lucy Chase Williams, author of The Complete Films of Vincent Price (Citadel Press, 1995). In early 1991, Tim Burton was developing a personal documentary with the working title Conversations With Vincent, in which interviews with Price were shot at the Vincent Price Gallery, but the project was never completed and was eventually shelved.[