On August 5, 2022, Heche was involved in a sequence of three motor vehicle collisions in the Mar Vista neighborhood of Los Angeles, the final crash being the most serious, inflicting critical injuries on Heche and destroying a house. The first collision took place when her vehicle struck an apartment garage and caused minor damage. A video released by TMZ shows her vehicle, a Mini Clubman, at the scene of the accident and an unidentified man repeatedly shouting "Out of the car!" at the driver. The vehicle then reversed and left the scene of the accident. A photo of the driver also released by TMZ is identified as Anne Heche. TMZ also reported a second hit-and-run in which Heche's vehicle struck a Jaguar without stopping, though without injury to the other driver. An accompanying video shows the Mini Clubman speeding down an alleyway and nearly hitting a pedestrian. A doorbell video recorded in the moments before the final crash shows Heche's vehicle driving along a neighborhood street at a very high speed, followed a few seconds later by the sound of a crash.
In the final crash, her vehicle struck a house, broke through a wall and embedded itself 30 feet into the building, trapping Heche inside. The vehicle caught fire, which rapidly spread through the entire building. The resulting house fire took 65 minutes to fully extinguish and required 59 firefighters. Firefighters were unable to access and fully extricate Heche from the vehicle for 45 minutes after their arrival on the scene, and initially were not aware that a person was trapped in the vehicle itself. Heche had sustained severe burns and smoke inhalation injuries by the time she was rescued. The house was left structurally compromised and uninhabitable. The tenant living in the house was in the rear of the structure at the time of the collision and only sustained minor injuries, but her attorney said that she and her pets "almost lost their lives" and that she had lost all of her personal property in the fire.
Law enforcement officials said that Heche was "deemed to be under the influence and acting erratically" at the time of the crashes. The Los Angeles Police Department said that a preliminary blood analysis confirmed the presence of both cocaine and narcotics, including fentanyl, in Heche's system, although a second and more comprehensive drug test is required to determine whether the narcotics detected were given by the hospital or ingested earlier. The second test could take anywhere from 30 to 90 days to complete.
As Heche was being removed from the crash scene, she was filmed sitting up on the stretcher and struggling with paramedics while she was being wheeled into the ambulance; however, she lost consciousness soon afterward. She was first taken to Ronald Reagan UCLA Medical Center for initial emergency care, and then to Grossman Burn Center at West Hills Hospital for speciaized burn center care. On August 8, a representative for Heche said that she was in a coma in critical condition, requiring medical ventilation for pulmonary injury sustained in the accident. The representative also said that prior reports that Heche was in "stable condition" were "inaccurate".
On August 11, the representative said that Heche was not expected to survive due to an anoxic brain injury she had sustained, but that she was being kept on life support to determine if her organs were viable for donation, in accordance with her expressed wish to be an organ donor. Heche was declared brain dead a few hours later, but remained on life support to assess organ donor viability and locate recipients. Having been declared "brain dead", Heche was considered legally dead at that time under California law.
On August 14, it was announced that organ recipients had been found and that her body would undergo the organ donation procedure that day. In honor for her organ donation, hospital staff held an honor walk for Heche. That evening, her publicist announced that she had been "peacefully taken off life support." The office of the Los Angeles County Medical Examiner-Coroner recorded the cause of death as "inhalation and thermal injuries", with "sternal fracture due to blunt trauma" listed as an "other significant condition", and ruled her death an accident.
Anne Heche's cremated remains were interred in a mausoleum at Hollywood Forever Cemetery on August 23, 2022.
On August 31, 2022, Heche's eldest son Homer Heche Laffoon filed a petition in the Los Angeles County probate court claiming that Heche had died intestate, and asking that he be named her estate's administrator. Laffoon's lawyer also stated that they wished to have a third party appointed guardian ad litem for Heche's younger son (and Laffoon's half-brother), Atlas Heche Tupper.
On September 15, Heche's former partner James Tupper filed a petition raising objections to Laffoon's. He argues that an email sent by Heche in 2011 describing her wishes in the event of her death should be treated as her will.
Tupper's petition challenges Laffoon's qualifications to administer the estate, claiming that at 20 years old, Laffoon lacks the maturity required of an administrator, and that Laffoon's lack of personal assets and income would render him unable to post the required bond. Tupper concludes that he wishes to act as executor and hire a professional fiduciary to manage the estate.