Her full-time acting career began in 1994 when she played Sarah Roberts in the ABC soap opera series One Life to Live until 1997.

She is the daughter of Lesley R. Vogel, a former soap opera actress, and Alan Lee "Skip" Panettiere, a captain in the New York City Fire Department.

She had one younger brother, fellow actor Jansen Panettiere, who died at age 28 from aortic valve complications from enlarged heart syndrome in 2023.

The Leukemia & Lymphoma Society gave her its Special Recognition Award for drawing the attention of daytime viewers to the disease, and for improving national awareness.

[14] Panettiere appeared on Fox's Ally McBeal as the title character's daughter, played the daughter of a man transitioning to female in HBO Films' Normal, had a recurring guest role on Malcolm in the Middle and guest starred in Law & Order: Special Victims Unit in two different roles.

Panettiere gained greater fame as Claire Bennet in the NBC series Heroes, which was created by Tim Kring, as a high school cheerleader with healing powers.

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 March 2012, it was announced Panettiere had been cast opposite Connie Britton on the ABC musical drama series Nashville, where she portrayed Juliette Barnes.

[19] Her first released film was the same year's The Object of My Affection at the age of 8, in which she appears briefly as a mermaid in the school play in the opening scene.

Her last major acting credit of 2004 was the role of adolescent niece to Kate Hudson's title character in Raising Helen, where Panettiere played the older sister to real life siblings Abigail and Spencer Breslin.

In 2006, Panettiere played a cheerleader in Bring It On: All or Nothing and had a supporting role as Adelaide Bourbon in the 2007 independent film Shanghai Kiss.

[21] In 2008, Panettiere appeared in the drama Fireflies in the Garden as a younger version of Emily Watson's character, Jane Lawrence.

In September 2008, she appeared in a satirical video, a mock-PSA for Funny or Die titled "Hayden Panettiere PSA: Your Vote, Your Choice".

[22] In October, Panettiere appeared in another satirical PSA video on funnyordie.com titled "Vote for McCain: He's just like George Bush, except older and with a worse temper".

Also in 2007, she sang the national anthem at A Capitol Fourth and recorded a cover for "Cruella De Vil" for Disneymania 5, "Try" for the Bridge to Terabithia soundtrack and a ballad called "I Still Believe" for Cinderella III: A Twist in Time.

[41][42][43] In 2009, Panettiere was one of the celebrities featured in the coffee table book Room 23,[44] produced by Diana Jenkins and photographed by Deborah Anderson.

[45] In 2007, Panettiere became an official supporter of Ronald McDonald House Charities and is a member of their celebrity board, called the Friends of RMHC.

[46] On October 31, 2007, Panettiere joined with The Whaleman Foundation to try to disrupt the annual dolphin hunt in Taiji, Wakayama, Japan.

She was involved in a confrontation between Japanese fishermen and five other surfers of the group from Australia and the United States (including former Home and Away actress Isabel Lucas).

[48] On January 28, 2008, Panettiere handed a letter of protest to the Norwegian ambassador in the U.S. arguing that Norway should stop its hunt for whales.

The auction included tickets to a fundraising dinner hosted at the Hollywood restaurant Beso, owned by Eva Longoria, and a whale watching tour, with Panettiere, off the coast of Santa Barbara.

[50] The same month, during an interview with Teen Vogue, she explained how her fame gives her a platform for her activism: "The show [Heroes] put me in a place to speak for things that I'm passionate about.

[55] In 2008, she appeared in a public service announcement with DC Shadow Senator Paul Strauss endorsing voting rights for Washington, D.C.[56] In 2011, DC Mayor Vincent Gray acknowledged Panettiere's advocacy on behalf of securing full representation in Congress for District of Columbia residents by naming a day in her honor.

On May 6, 2009, she participated in a town hall meeting in New York City alongside Bristol Palin and Major League Baseball pitcher Matt Garza on the issue of teen pregnancy.