Educated at the National Theatre School in Denmark, Nikolaj shot to fame with his performance in the Danish thriller Nightwatch in 1994.

His U.S career began with a starring role in Ridley Scott’s Academy Award-winning Black Hawk Down followed by a lead role in Enigma co-starring with Kate Winslet in 2001. Scott also cast him again as the village Sheriff in epic film Kingdom of Heaven in 2005 and he starred in Richard Loncraine’s rom-com Wimbledon (2004) and then again in Loncraine's thriller Firewall (2006). 

Recently Nikolaj has played a New York homicide detective in the Fox drama series New Amsterdam and starred in TV mini series Blekingegade. Currently Nikolaj is filming Mateo Gil's Blackthorn and has also been cast in the HBO series Game of Thrones based on George R. R. Martin's series of fantasy novels A Song of Fire and Ice.