After Braveheart won Best Picture at the Academy Awards, Macfadyen acted in the independent film Nevada (1997), before giving the most over-the-top[citation needed] performance of his career in the action/fantasy Warriors of Virtue (1997).

He also co-starred alongside Don Cheadle and Ray Liotta when he played Peter Lawford in the HBO film The Rat Pack (1998).

A year later, he acted in the comedy film Divine Secrets of the Ya-Ya Sisterhood (2002) alongside a number of famous names: Sandra Bullock, Ellen Burstyn, Maggie Smith and Ashley Judd.

The film, also starring Christian Bale, Sean Bean, Taye Diggs and Emily Watson, is set in the future, where a fascist regime forbids all emotions.

[3] Macfadyen acted as Marcus Crassus in a TV mini-series of Spartacus (2004), and the character of Bill in The Pleasure Drivers (2005).

[3] He then starred in Kevin Connor's mini-series Blackbeard, it co-stars Richard Chamberlain, Jessica Chastain, Mark Umbers, Stacy Keach, David Winters, and Rachel Ward.

Additionally, Macfadyen was part of the cast of the USA Network's television series Psych, the Cameron Crowe feature film We Bought a Zoo (2011) starring Matt Damon, and the final season of Chuck as villain Nicholas Quinn.

[6] He appeared opposite Charlie Hunnam and Robert Pattinson as biologist James Murray in the 2016 biographical drama The Lost City of Z.