She began her acting career by playing Sarah Roberts on One Life to Live (1994–97), and Lizzie Spaulding on Guiding Light (1996–2000), before starring at age 10 as Sheryl Yoast in the Disney feature film Remember the Titans.
While on Guiding Light, Panettiere's character Lizzie battled leukemia.
Panettiere made her feature film debut with 1998's A Bug's Life, but her first film to actually be released was the same year's The Object of My Affection, in which she appears briefly as a mermaid in the school play in the opening scene.
In 1999, she portrayed the girl on a sinking sailboat in Message In A Bottle.
She has Italian, and some English and German ancestry.
She has one younger brother, fellow actor Jansen Panettiere.