Her breakthrough came with playing Sydney Bristow in the ABC action thriller series Alias (2001–2006), which earned her a Golden Globe, and four Primetime Emmy Award nominations, among other honors.

Garner received further recognition for her starring roles in the romantic comedies 13 Going on 30 (2004), Juno (2007), Ghosts of Girlfriends Past (2009) and Valentine's Day (2010), and for playing Elektra in superhero films, including Daredevil (2003).

[11] As teenagers, she and her sisters were not allowed to wear makeup, paint their nails, pierce their ears, or dye their hair;[12][13] she has joked that her family's "take on the world" was "practically Amish".

[15] In 1990, Garner enrolled at Denison University in Granville, Ohio,[16] where she changed her major from chemistry to theater[17] and was a member of the sorority Pi Beta Phi.

[27] During her first year in the city, Garner earned $150 per week as an understudy for a Roundabout Theatre Company production of A Month in the Country[8][28] and made her first on-screen appearance as Melissa Gilbert's daughter in the romance miniseries Zoya.

In 2001, she appeared briefly opposite her husband Scott Foley in the drama Stealing Time and had a small role as a nurse in the war epic Pearl Harbor.

"[58] Ann Hornaday of The Washington Post remarked: "Garner is clearly cut out to be America's next Sweetheart; she has the same magic mix of allure and accessibility that the job calls for.

[28] Ben Brantley of The New York Times described her performance as "captivating": "Ms. Garner, I am pleased to report, makes Roxane a girl worth pining over ... [She] speaks Anthony Burgess's peppery rhymed translation with unaffected sprightliness.

[75] Similarly, Manohla Dargis of The New York Times was dismayed to see Garner appear as "less a co-star than a place holder (you can almost see the words "enter generic female lead" in [the] screenplay)".

"[80] In Garry Marshall's ensemble romantic comedy Valentine's Day (2010), Garner shared scenes with Ashton Kutcher, Jessica Biel, and Patrick Dempsey.

[81] In 2011, she had a supporting role as a villainous deranged bride in the comedy Arthur, a remake of the 1981 film of the same name, directed by Jason Winer and co-starring Russell Brand and Helen Mirren.

[82][83] Garner played a mother for the first time in 2012,[7] in the drama The Odd Life of Timothy Green, which followed a magical pre-adolescent boy whose personality and naïveté have profound effects on the people in his town.

[85][86] Claudia Puig of USA Today found Garner "convincing as a warm-hearted, if tense, mom"[87] while Michael Phillips of the Chicago Tribune said she brought "fervent sincerity and a welcome touch of comic eccentricity" to the role.

"[92] However, Scott Bowles of USA Today remarked: "Garner is a terrific actress, but here she's asked to cackle her lines in a voice a full octave above her natural one.

[95] Garner reunited with Matthew McConaughey in the 2013 biographical drama Dallas Buyers Club, portraying the role of a doctor treating AIDS patients in Texas during the mid-1980s.

Critical reception toward the film was mixed and Mick LaSalle of The San Francisco Chronicle, describing her part, remarked: "It's not much of a role, but she's perfectly nice in it.

"[103] Garner also co-starred with Steve Carell in the 2014 Disney adaptation of the popular children's book Alexander and the Terrible, Horrible, No Good, Very Bad Day, taking on the role of the mother of the titular character.

[104] Sandie Angulo Chen of the Washington Post said: "Garner, who has long mastered the art of playing harried and overworked moms, is pleasantly frazzled.

"[105] Her other film role in 2014 was that of an overprotective mother in the dramedy Men, Women & Children, directed by Jason Reitman and co-starring Rosemarie DeWitt, Judy Greer, Dean Norris, and Adam Sandler.

[108] In 2015's Danny Collins, a drama inspired by the true story of folk singer Steve Tilston and starring Al Pacino and Annette Bening, Garner played the supporting role of the wife of Bobby Cannavale's character.

The film was released in selected cinemas and was warmly received by critics; Stephanie Merry of The Washington Post felt Garner gave the movie "a powerful jolt of emotion".

[109] In 2016, Garner appeared in the Christian drama Miracles from Heaven, playing the mother of a young girl who had a near-death experience and was later cured of an incurable disease.

[111] Ken Jaworowski of The New York Times praised a "dedicated" and "heartfelt" performance,[112] while Nigel Smith of The Guardian found "her subtly wrought work ... tremendously effective" in an otherwise "crassly manipulative" film.

[113] Also in 2016, Garner starred in the critically panned comedy Nine Lives, playing the second wife of a workaholic father who has his mind trapped inside of his daughter's new cat.

In 2020, Garner starred in the Quibi comedy miniseries Home Movie: The Princess Bride, a "fan made" recreation of the 1987 film of the same name produced in social isolation during the COVID-19 pandemic.

[124] Also that year, Garner executive produced and starred as Hannah Hall in the Apple TV+ limited mystery drama series The Last Thing He Told Me, which is based on the novel of the same name.

Also that year, it was revealed that Garner would reprise her role as Elektra Natchios in the Marvel Cinematic Universe superhero film Deadpool & Wolverine, which was released on July 26, 2024.

[126] In a 2002 episode of the action thriller series Alias, titled "Rendezvous", Garner sang a version of the song "Since I Fell For You", to which she wrote her own lyrics.

She also sang "My Funny Valentine" when hosting a 2003 episode of the sketch comedy series Saturday Night Live, on which Beck was the musical guest; she was not credited for either performance.

[138] In 2002, Garner filmed a 30-second television advertisement for her childhood friend Corey Palumbo, who was running as a Democratic candidate for the West Virginia House of Delegates.