Nancy Guthrie, the 84-year-old mother of NBC Today show presenter Savannah Guthrie, is believed to have been abducted from her home.
Mrs Guthrie is said to have been taken against her will from her Arizona residence on Saturday evening.
The elderly woman vanished from her home in the affluent Catalina Foothills area near Tucson around 9.45pm local time.
Pima County Sheriff Chris Nanos has confirmed that a major search operation is now underway.
"I believe she was abducted," Mr Nanos told CBS News.
Her family raised the alarm the following day after she failed to appear at church.
Authorities are treating her $1million property as a crime scene, with investigators racing to locate her.
Mr Nanos revealed that Mrs Guthrie requires medication to survive and faces potentially fatal consequences without it after 24 hours.
The sheriff noted that the pensioner is physically unable to travel "more than 50 yards on her own" but remains mentally "sharp as a tack", ruling out dementia as a factor.
Last year, the broadcaster paid tribute to her mother on Instagram for Mother's Day, describing her as 'God's first, best and most important gift to me'
|INSTAGRAM/SAVANNAHGUTHRIE
"I can't think of the last time where in the middle of the night in someone's bed, an 84-year-old woman disappeared on us," he added.
"We believe she was taken out of the home against her will, and that's how this investigation is moving."
Her mobile phone, wallet and vehicle were all discovered at the property.
Helicopters equipped with infrared cameras are now scanning the surrounding terrain alongside drone units.
LATEST US CELEBRITY HEADLINES:
Police have issued a missing persons poster in their bid to find Nancy Guthrie
|PIMA COUNTY SHERIFF'S OFFICE
Teams of volunteers have joined the effort to locate the missing woman.
Customs and Border Patrol officers, stationed approximately 75 miles from the Mexican border, have provided search-and-rescue dogs to assist.
Mr Nanos has appealed to residents in the Catalina Foothills to review their security cameras and doorbell footage for any relevant information.
"It's a very safe neighbourhood. This is highly unusual, and we are very concerned about her," neighbour Jeff Lamie told local media.
Savannah Guthrie did not present the Today show on Monday - and later thanked followers for their thoughts, prayers, and messages of support
|GETTY
The area is considered one of Arizona's most affluent communities.
Savannah Guthrie, who has presented NBC's flagship morning programme since 2012, did not appear at work on Monday.
She released a statement expressing gratitude "for the thoughts, prayers, and messages of support".
"Right now, our focus remains on the safe return of our dear mom," she continued. "We thank law enforcement for their hard work on this case and encourage anyone with information to contact the Pima County Sheriff's office."
Last year, the broadcaster paid tribute to her mother on Instagram for Mother's Day, describing her as "God's first, best and most important gift to me".