In 2004, Seyfried made her film debut in Mean Girls playing Karen Smith, the ditsiest of the so called 'Plastics'. She then went on to other films including Nine Lives (2005) and Alpha Dog (2006). In 2006, she landed a lead role on HBO's popular television series Big Love. After that, Seyfried appeared as Sophie Sheridan in the 2008 musical feature film Mamma Mia!. Other recent notable appearances include lead roles in Jennifer's Body and Chloe in 2009, and one of the two lead roles in Dear John the following year.

Seyfried was born Amanda Michelle Seyfried in Allentown, Lehigh County, Pennsylvania on December 3, 1985. Seyfried's mother, Ann (née Sander), was an occupational therapist, and her father, Jack, was a pharmacist. Seyfried has one older sister, Jennifer Seyfried, who is a musician in the Philadelphia organ-driven rock band Love City. Seyfried graduated in 2003 from Allentown's William Allen High School.

I was naturally skinny and had braces, so I wasn't a cute model. I never felt pretty but it was fun and I got a cool pay check to buy sweets with.

In 1995, Seyfried began her acting career at age nine, in her hometown Allentown, Pennsylvania where she attended classes at Civic Theatre of Allentown. When Seyfried was 11, she signed with Image International Agency (IIA) in Allentown, before switching over to work at Bethlehem's Pro Model Agency and eventually signing with Wilhelmina Agency in New York City, New York. Seyfried's modeling career ended when she was seventeen. During her modeling career she appeared in print ads for clothing companies; including Limited Too with Leighton Meester.

While modeling, Seyfried took voice lessons from eleven to seventeen. She trained with a Broadway voice coach for nearly five years and studied opera for two years which led to her appearance in the New York stage productions, the revival of Grease on Broadway and A Christmas Carol. From there she began acting as an extra in the daytime drama television series Guiding Light; her role on the show was uncredited. In 2000, she portrayed Lucinda Marie "Lucy" Montgomery#2 on the television show As the World Turns. Appearing on the show as a recurring character, her role on the show lasted until 2001. After appearing in 27 episodes, Seyfried left the show as a result of creative conflicts. From 2002 to 2003, Seyfried played the recurring role of Joni Stafford on the American Broadcasting Company (ABC) broadcasted show, All My Children. In 2003, Seyfried auditioned to play the mean-girl role of Regina George in the Mean Girls starring Lindsay Lohan; the role eventually went to Rachel McAdams. However, she was initially considered to play Cady Heron but the producers of the film decided that Seyfried should play Karen Smith, one of Regina's two dim-witted "Plastic" friends and sidekicks. The film was a box-office success, earning over $129 million in its theatrical run. Seyfried's performance in the film earned her, along with Lohan and McAdams, an MTV Movie Award in the category of "Best On-Screen Team."

Seyfried auditioned to play the title character on UPN's television series Veronica Mars. Although the role eventually went to Kristen Bell, Seyfried portrayed the title character's murdered best friend, Lilly Kane. Although her character was only shown in flashbacks, Lily was vital part of the first season's plot and made Seyfried one of the show's familiar faces. Seyfried appeared in ten episodes from 2004–2005. In 2005, Seyfried played the lead character, Samantha, a role written specifically for her, in one of the nine parts in the film Nine Lives, comprising nine short films with different themes and an ensemble cast. For her performance in the film, Seyfried won an award from the Locarno International Film Festival, for Best Actress, which she shared with the film's other female leads. The same year she played supporting character Mouse in the critically acclaimed independent film, American Gun. In 2006 Seyfried appeared in five episodes on Wildfire as Rebecca and had lead role as Chrissy in the award winning short film titled Gypsies, Tramps & Thieves, by writer-director Andrea Janakas. Seyfried also contributed a minor role as Julie Beckley in Alpha Dog. From 2004 to 2006, Seyfried made multiple guest appearances on television series, including House, M.D., Justice, Law & Order: Special Victims Unit and CSI: Crime Scene Investigation. In 2008, Seyfried also appeared and played a supporting role in the independent short film, Official Selection.

Seyfried's profile gained prominence due to her role in the highly acclaimed HBO drama television series, Big Love. The series centers on a fictional fundamentalist Mormon family, in which Seyfried plays Sarah Henrickson, Bill and Barb's first daughter who struggles with her family's polygamous faith. Big Love premiered in the United States on March 12, 2006. HBO confirmed that the show was renewed for a fourth season – which was filmed in August 2009, and premiered on January 10, 2010. Seyfried appeared in all 35 episodes of the show's three seasons. In December 2009, HBO confirmed that Seyfried would return for the show's fourth season, but that it would be her last, as Seyfried wished to focus on her film career and upcoming projects.

Following the success of Big Love, Seyfried had a supporting role as Zoe in the 2008 horror drama film Solstice. Also in 2008, she co-starred alongside Meryl Streep in Mamma Mia!, a romantic comedy film adaptation of the 1999 musical of the same name. Mamma Mia! was Seyfried's first leading role as Sophie. With worldwide revenue of US$609 million (of a US$52 million budget), the film was the fifth highest grossing film of 2008 and, as of March 2010, is the 49th highest grossing film of all time. Wesley Morris of the Boston Globe commented that "what Seyfried lacks in emotional range is compensated for in luminousness". Her musical performance in Mamma Mia! was released on the film's soundtrack, for which she recorded five songs. As part of promotion for both the film and its soundtrack, Seyfried recorded a music video of the song, entitled "Gimme! Gimme! Gimme! (A Man After Midnight)".

On February 22, 2009, Seyfried presented an award and performed alongside her boyfriend, Dominic Cooper, actors Hugh Jackman and Zac Efron, and musicians Beyoncé Knowles and Vanessa Hudgens at the 2009 Annual 81st Academy Awards ceremony. In March 2008, Seyfried signed on to co-star alongside Megan Fox and Adam Brody in the comedy horror film Jennifer's Body. In the film Seyfried was cast as Anita "Needy" Lesnicki, the title character's best friend. The film, which premiered at the 2009 Toronto International Film Festival and was released to theaters on September 18, 2009, received mixed reviews from critics. Robert Abele of the Los Angeles Times wrote in his review for the film "...but thankfully the part of Needy has been tasked to the appealing Amanda Seyfried, an actress able to reach past Cody's tone-busting one-liners and connect on a basic what-the-hell-happened-to-my-friend level." Kurt Loder of MTV wrote that Seyfried "is just right" as Jennifer's best friend Needy in Jennifer's Body.

In early March 2009, director Zack Snyder had tapped Seyfried to portray the lead role Baby Doll in Sucker Punch. Seyfried was due to co-star alongside Vanessa Hudgens, Abbie Cornish, Emma Stone and Evan Rachel Wood, but within the same month, she—along with Evan Rachel Wood and Emma Stone–had to drop out of the film due to scheduling conflicts. Seyfried's coincided with her HBO drama Big Love Emily Browning was then later cast in the role of Baby Doll. Seyfried co-starred alongside Channing Tatum in Dear John, the film adaptation of the novel of the same name that was written by Nicholas Sparks. The film was released on February 5, 2010, and received generally negative reviews, although Melissa Anderson of LA Weekly praised Seyfried and Tatum's on screen chemistry. However, Michael O'Sullivan of the Washington Post was less enthusiastic about Seyfried's performance, stating that while she "otherwise makes a credible love interest," she could not convince him "that she had to do what she did." Stephanie Zacharek of Salon.com, describing Seyfried's character as being potentially sweet and marvelously direct, felt that those were two qualities were held in balance perfectly by Seyfried. Spotlighting her musical talents, Seyfried has written and recorded "Little House", a song which appears on one of the official soundtracks of Dear John. Despite many negative reviews, Dear John became the first film to break up Avatar's box office reign at number one at the United States box office and went on grossing $80 million in the US theatrically.