Robert Downey Jr. (Sherlock Holmes), Jude Law (Dr. John Watson), Jared Harris (Professor James Moriarty), Noomi Rapace (Madame Simza Heron), Stephen Fry (Mycroft Holmes), Rachel McAdams (Irene Adler), Paul Anderson (Colonel Sebastian Moran), Eddie Marsan (Inspektor Lestrade), Kelly Reilly (Mary Watson), Thierry Neuvic (Claude Ravache), William Houston (Constable Clark), Geraldine James (Mrs. Hudson), Wolf Kahler (Doktor Hoffmanstahl), Iain Mitchell (Auktionator), Jack Laskey (Carruthers), Richard Cunningham (Geschäftsmann), George Taylor (Student), Michael Webber (Vikar), Thorston Manderlay (Alfred Meinhard)