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Cox trained at the Dundee Repertory Theatre before becoming a founding member of the Royal Lyceum Theatre. He went on to train as a Shakespearean actor, starring in numerous productions with the Royal National Theatre and the Royal Shakespeare Company, where he gained recognition for his portrayal of King Lear. Cox received two Laurence Olivier Awards for Best Actor for his roles in Rat in the Skull (1984), for Royal Court, and Titus Andronicus (1988). He received two more Olivier Award nominations for Misalliance (1986) and Fashion (1988).

Known as a character actor in film, he played Robert McKee in Spike Jonze's Adaptation (2002) and William Stryker in X2 (2003). For his starring role in L.I.E. (2001), he received an Independent Spirit Award nomination. His other notable films include Manhunter (1986), Iron Will (1994), Braveheart (1995), The Boxer (1997), The Rookie (2002), Troy (2004), Match Point (2005), The Water Horse: Legend of the Deep (2007), Coriolanus (2011), Pixels (2015), and Churchill (2017).

Cox won the Primetime Emmy Award for Best Supporting Actor in a Limited Series for his portrayal of Hermann Göring in the television film Nuremberg (2001). The following year, he guest starred on the NBC sitcom Frasier, earning his second Emmy nomination in 2002. He portrayed Jack Langrishe in the HBO series Deadwood. He starred as Logan Roy on the HBO series Succession (2018-2023), for which he won the Golden Globe Award for Best Actor in a Drama Series and was nominated for three Primetime Emmy Awards for Best Actor in a Drama Series.