The beloved musician's system showed traces of fentanyl, oxycodone, temazepam, alprazolam, citalopram, acetylfentanyl and despropionyl fentanyl, according to a statement from Jonathan Lucas, the chief medical examiner for the coroner's office.
Petty's wife Dana and daughter Adria said the medical examiner told them he "passed away due to an accidental drug overdose as a result of taking a variety of medications".
Although it was reported that Petty had suffered a cardiac arrest when he died last fall, the cause of death on his death certificate read "deferred".
The family stated in the statement that Petty was prescribed the drugs to treat emphysema, knee issues and a fractured hip.
Petty, whose ringing guitar riffs, distinctive vocals and well-wrought everyman lyrics graced such hits as Refugee, Free Fallin and American Girl, was found unconscious at his home in Malibu on October 2 and died at a hospital later that night.
They added that his death "may spark a further discussion on the opioid crisis and we feel that is a necessary and healthy discussion".
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Music legend Prince, who was also reported to have suffered from hip pain, died previous year from a fentanyl overdose and may have unwittingly taken the drug.
Petty had talked about his drug problems in the past.
A 2015 biography of Petty revealed for the first time that he was addicted to heroin in the 1990s.
"Tried to go cold turkey, and that wouldn't work", Petty said in the book.
"He and the band were inducted into the Rock and Roll Hall of Fame in 2002, when they were described by organizers as 'the quintessential American individualists", capturing the voice of the American everyman.
The toxicology report of Tom Petty was released Friday, coming almost four months after the beloved rock musician passed away in October. He joined fellow music legends Dylan, George Harrison, Jeff Lynne and Roy Orbison in 1988 to form The Traveling Wilburys. It concluded September 25 with a three-night homecoming stand that sold out at the Hollywood Bowl.