She was 3 years of age when she began learning dance. Whenever she was 13, her family moved to Los Angeles and, subsequently, started Annette O’Toole’s acting interests.

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She showed up as a bystander in the 1970 Western film Little Big Man. Nonetheless, her job went uncredited. For her depiction of Rose Fitzgerald Kennedy in The Kennedys of Massachusetts, Annette was designated for a Primetime Emmy Award for “Remarkable Lead Actress in a Limited or Anthology Series or Movie”.

In 2012, she was seen playing the person named Elaine Sherman in an episode named The Boy with the Bucket of the procedural show series The Finder.

Annette O’Toole was drafted into the Texas Film Hall of Fame in Austin, Texas on March 7, 2013. In March 2013, she showed up as Madeleine Skurski in an episode named Idle Hands of the clinical dramatization series Gray’s Anatomy. She co-featured as Lila in the 2016 satire thrill ride film Women Who Kill. Weaving has been one of her side interests.