Nighy has starred in many radio and television dramas, notably the BBC serial, The Men's Room, opposite Harriet Walter.

His films include Eye of the Needle, Curse of the Pink Panther, The Phantom of the Opera, Mack the Knife, Being Human, True Blue, Indian Summer, FairyTale: A True Story, Still Crazy, Guest House Paradiso, Blow Dry, The Lawless Heart, AKA, Lucky Break, I Capture the Castle, Underworld, and Love Actually.