On September 7, 2018, Miller was found unresponsive in his Studio City home by his personal assistant, who called 911 and performed CPR until paramedics arrived. Miller was pronounced dead at the scene at 11:51 a.m. (PDT). He had been scheduled for a video shoot on the day of his death, and was to embark on his Swimming Tour in October. In his will, Miller named his mother, father, and brother as beneficiaries. He was buried at Homewood Cemetery in his hometown of Pittsburgh, in a Jewish funeral. On November 5, 2018, the Los Angeles County Coroner's office determined that Miller died from an accidental drug overdose due to a "mixed drug toxicity" of fentanyl, cocaine, and alcohol.

Thousands of fans held a vigil for Miller on September 11, 2018, at Pittsburgh's Blue Slide Park, the inspiration behind his debut album title; the site continues to be a place of remembranceand is now called 'Mac Miller's Blue Slide Park'. A tribute concert, Mac Miller: A Celebration of Life, took place on October 31, 2018, in Los Angeles. Many of his friends and collaborators performed or provided messages at the concert; proceeds raised benefited the newly-established Mac Miller Circles Fund, which aims to support youth arts and community-building programs in his memory. The charity had raised over $700,000 by January 2019. In May 2019, the renamed Mac Miller Fund issued its first grants, including $50,000 to MusiCares, which was used to launch their Mac Miller Legacy Fund to help young musicians with substance abuse issues.

Three men were arrested in September 2019 during an investigation into Miller's death. Cameron James Pettit allegedly sold Miller counterfeit oxycodone pills containing fentanyl two days before his death, which were run to Pettit by Ryan Reavis and supplied by Stephen Walter. Miller had asked Pettit for Percocet, a prescribed painkiller containing oxycodone, in addition to cocaine and Xanax. Investigators believe Miller snorted the laced pills before his death. The three men were indicted on charges of conspiracy and distribution of drugs resulting in death.