In 1999, she portrayed the girl on a sinking sailboat in Message In A Bottle.
She played the role of Coach Yoast's daughter, Sheryl, in the 2000 Disney film Remember the Titans.
In April 2012, she hosted an episode of the new series.
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.
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.