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.
The same year she replaced Anne Hathaway as the voice of Red for the animated sequel Hoodwinked Too! While she was replaced by Alyson Stoner in Kingdom Hearts Re: Chain of Memories and Kingdom Hearts 358/2 Days, she reprised her role in Kingdom Hearts Birth by Sleep and also voiced Xion in Kingdom Hearts 3D: Dream Drop Distance.
In 2004, she recorded a song entitled "My Hero Is You" with a video for the Disney Channel film she starred in, Tiger Cruise, and "Someone Like You," a duet with Watt White for another film, The Dust Factory (also with an accompanying video).
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 received two nominations for the Golden Globe Award for Best Supporting Actress – Series, Miniseries or Television Film, for her work on Nashville in 20.