Vanessa Marquez, 49, who played nurse Wendy Goldman in the NBC show, died after pulling a “realistic” BB gun on officers in South Pasadena, California on Thursday.
Police were initially called to Marquez’s home amid reports a woman, later identified as the actress, was having seizures.
Lieutenant Joe Mendoza said three officers and a mental health care worker spent 90 minutes trying to give her aid, during which Marquez was “extremely uncooperative”.
Police said Marquez pointed what looked like a handgun at the officers, who opened fire.
Reports said the actress was struck at least once in the torso and died in hospital.
Marquez is best known for her role in ER with Clooney from 1994 to 1997.
Last year she accused him of helping blacklist her after she spoke out about alleged harassment on the ER set.
Clooney insisted he had no idea she had been blacklisted and had played no part in it.