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.
Other notable roles include her portrayal of the title character in the true crime drama Amanda Knox: Murder on Trial in Italy and Kirby Reed in the slasher film Scream 4.
In March 2012, it was announced Panettiere had been cast opposite Connie Britton on the ABC musical drama series Nashville. The pilot reunites Panettiere with Burgess Jenkins (who appears in the first few episodes) from Remember the Titans.
ABC canceled the series in May 2016 but it was later picked up by CMT and Hulu for a fifth season.
She is known for her roles as cheerleader Claire Bennet on the NBC sci-fi series Heroes (2006–10), Juliette Barnes in the ABC/CMT musical-drama series Nashville (2012–present) and Kairi in the video game series Kingdom Hearts.
A native of New York, she first appeared in a commercial at the age of 11 months.
Panettiere has complained that her acting options are sometimes limited because "people look at [her] as either the popular cheerleader type or just the blonde".
In early 2007, Panettiere appeared on the MTV show, Punk'd.Panettiere became most prominent as Claire Bennet in the NBC series Heroes, which was created by Tim Kring, as a high school cheerleader with regenerative healing powers.Thanks to her role on Heroes, she became a regular on the science fiction convention circuit, invited to attend conventions around the world in 2007, including Gen Con, New York Comic Con, and Fan Expo Canada.The appearance was engineered by her mother and involved a male "fan" discussing her work with her, instigating a jealous reaction from the man's spouse.In April 2012, she hosted an episode of the new series.In 2005, she was the title character's rival in a skating contest in Ice Princess.