His films include Troy (2004), Friday Night Lights (2004), Four Brothers (2005), Eragon (2006), Death Sentence (2007), Tron: Legacy (2010), Country Strong (2010), On the Road (2012), Inside Llewyn Davis (2013), Unbroken (2014), Pan (2015), Mudbound (2017), Triple Frontier (2019), and The Marsh King's Daughter (2023).

[23][24] He co-starred with Ed Speleers, Jeremy Irons, Djimon Hounsou and John Malkovich in the fantasy / adventure film Eragon as Murtagh Morzansson.

[27] In 2007, he co-starred with Lindsay Lohan, Jane Fonda and Cary Elwes in the comedy Georgia Rule, directed by Garry Marshall.

[30] In 2010, Hedlund played Sam Flynn, the main protagonist in the science fiction / action film Tron: Legacy, acting alongside Jeff Bridges and Olivia Wilde.

[31] Hedlund won a "Darwinian casting process" which tested hundreds of actors, being chosen for having the "unique combination of intelligence, wit, humor, look and physicality" that the producers were looking for in Flynn's son.

[34][35] Hedlund was also considered by Disney to play Captain America / Steve Rogers in the Marvel Cinematic Universe,[36] but had to abandon the project because his film schedule got in the way of Tron: Legacy.

[38] He recorded a number of songs for the film including "Chances Are" which appeared on Country Strong: Original Motion Picture Soundtrack.

[41][42] He also co-starred with Kristen Stewart, Sam Riley, Kirsten Dunst and Viggo Mortensen as Dean Moriarty in the 2012 adventure drama On the Road,[43] produced by Francis Ford Coppola.

In The Hollywood Reporter, veteran reviewer Todd McCarthy writing "Although the story is Sal / Kerouac's, the star part is Dean, and Hedlund has the allure for it; among the men here, he's the one you always watch, and the actor effectively catches the character’s impulsive, thrill-seeking, risk-taking, responsibility-avoiding personality.

"[46] Entertainment Weekly magazine's Owen Gleiberman wrote, "The best thing in the movie is Garrett Hedlund's performance as Dean Moriarty, whose hunger for life – avid, erotic, insatiable, destructive – kindles a fire that will light the way to a new era.

[52] In 2013, Hedlund co-starred with Oscar Isaac, Justin Timberlake and Adam Driver in the French-American black comedy-drama film Inside Llewyn Davis, directed by Joel and Ethan Coen.

[53] Hedlund pays homage to a fallen cowboy whose name is Lane Frost in the music video of the song Beautiful War by American rock band Kings of Leon.

[54] Also in 2013, he was the image of Yves Saint Laurent Beauté's French men's fragrance "La Nuit de l'Homme".

[63][64] Also that same year, he co-starred with Sharon Stone as an aspiring artist in Steven Soderbergh's HBO murder mystery drama series Mosaic.

[68] He co-starred with Ben Affleck, Oscar Isaac, Charlie Hunnam, and Pedro Pascal in the action / adventure film, released by Netflix in 2019 and directed by J. C. Chandor, Triple Frontier recorded between Soacha and Bogotá, where he plays a former Special Forces Soldier in a particular mercenary operation in South America.

[78] That same year, he co-starred with Sylvester Stallone in the Paramount+ series Tulsa King, playing bartender and ex-bull rider Mitch Keller.

[81] This same year, he also co-starred with Daisy Ridley and Ben Mendelsohn in the film The Marsh King's Daughter, directed by Neil Burger and based on the international bestseller by Karen Dionne.