The Trainspotting star, most recently seen in BBC series Girl/Haji, will play Detective Chief Inspector Joanne Davidson, the senior investigating officer of an unsolved murder, whose unconventional conduct raises suspicions at AC-12.
She'll be investigated by superintendent Ted Hastings (Adrian Dunbar), DS Steve Arnott (Martin Compston) and DS Kate Fleming (Vicky McClure), who'll all return for the sixth series.
The show's creator Jed Mercurcio said: "We're honoured that Kelly Macdonald will join Martin, Vicky and Adrian in series six of Line of Duty. DCI Joanne Davidson will prove the most enigmatic adversary AC-12 have ever faced."
Line of Duty's series five finale was the most-watched episode of the year so far, amassing more than 13.5m viewers in the UK.
Each series focuses on a new character to be investigated by the team. The most recent outing focused on Stephen Graham's character, John Corbett.
There's currently no word on when the new series will arrive.
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