He has appeared in several Australian films, such as The Square (2008), Animal Kingdom (2010; for which he received the AACTA Award for Best Supporting Actor), Wish You Were Here (2012), and Felony (2013).

Edgerton's other film appearances include King Arthur (2004), Legend of the Guardians: The Owls of Ga'Hoole (2010), Warrior (2011), Zero Dark Thirty (2012), The Great Gatsby (2013), Black Mass (2015), Bright (2017), Red Sparrow (2018), The Green Knight (2021), The Stranger, Thirteen Lives, and Master Gardener (all 2022), and The Boys in the Boat (2023).

In the Star Wars franchise, he played a young Owen Lars in Attack of the Clones (2002) and Revenge of the Sith (2005)[7] and reprised the role in the Disney+ series Obi-Wan Kenobi.

In 2005, he lent his voice to the title character of The Mysterious Geographic Explorations of Jasper Morello, an Academy Award-nominated animated short film.

[13] He appeared in the crime drama film Animal Kingdom as Barry Baz Brown in 2010 in which he won an AFI award.

[14][15] In February 2010, Edgerton was cast in Matthijs van Heijningen Jr.'s 2011 prequel to The Thing,[16] portraying helicopter pilot Sam Carter.

[22] He co-starred in the 2015 film Black Mass as John Connolly, FBI contact and childhood friend of notorious gangster Whitey Bulger.

In February 2018, Timothée Chalamet joined the cast of The King, with Brad Pitt, Dede Gardner, and Jeremy Kleiner producing, alongside Liz Watts, under their Plan B Entertainment banner.

In September 2020, Edgerton was tapped to star in and executive produce limited series The Florida Man based on a novel of the same name by Tom Cooper.

Edgerton has been a distinguished ambassador for The Fred Hollows Foundation for a number of years and has strong personal ties to the organisation, which works to restore people's sight in poor countries and to improve the health of Aboriginal Australians.

[38] The Fred Hollows Foundation is an international non-profit organisation which educates and provides equipment for under-supported surgeons to help cure avoidable blindness.