A 14-year-old girl discovered her mother shot dead behind the wheel of her car, more than a year after finding her father and sister murdered in their apartment.
The latest attack appeared to be connected to the earlier killings, Los Angeles police said.
Karine Hakobyan, 38, a nursing assistant at Childrens Hospital, was found on Friday in her Honda CRV with a gunshot wound to the back of her head.
Detectives investigating the killing of her husband Khachik Safaryan, 43, and their nine-year-old daughter Lucine said there appeared to be a link to the crimes.
"We're working on a theory that was developed in the previous homicides," Detective Dan Myers said.
He did not provide further details but said none of the Armenian victims had any criminal associations.
In both cases, the bodies were discovered by another daughter in the family, Detective Myers said.
Police had been in regular contact with Mrs Hakobyan during their first investigation.
Detective Myers went to her apartment last week then got a call on Friday saying she was dead.
"It's horrible," he said. "You meet a victim, you spend a lot of time together, then you get a call in the middle of the night saying she's been murdered."
Police have developed few leads in any of the shootings, despite a £50,000 reward offered for information about the killing of Mr Safaryan and his daughter in their family home on 11 December, 2008.
Shortly after those killings, the mother and her surviving daughter moved to her in-laws in a nearby apartment complex.
Neighbours said they were shocked by the attack on Mrs Hakobyan in the complex they described as mostly family friendly and secure.
A woman at the apartment of Hakobyan's in-laws said the couple was too upset to speak.
The woman, who would not give her name, said Mrs Hakobyan kept her feelings to herself but struggled with the deaths of her husband and daughter and frequently visited a nearby memorial park.
The Hakobyans married in Armenia and moved from the capital city of Yerevan to the US in 2003, Detective Myers said.