 | Ian McKellen als Sherlock Holmes |
 | Laura Linney als Mrs. Munro |
 | Milo Parker als Roger |
 | Hiroyuki Sanada als Tamiki Umezaki |
 | Roger Allam als Dr. Barrie |
 | Frances de la Tour als Madame Schirmer |
 | Hattie Morahan als Ann Kelmot |
 | Phil Davis als Inspector Gilbert |
 | Patrick Kennedy als Thomas Kelmot |
 | John Sessions als Mycroft Holmes |
 | Frances Barber als Matinee "Madame Schirmer" |
 | Charles Maddox als Oswald |
 | Takako Akashi als Maya Umezaki |
 | Zak Shukor als Masuo Umezaki |
 | Michael Culkin als Bank Manager |
| David Foxxe als Chemist |
 | Oliver Devoti als Ticket Agent |
| Mike Burnside als Ann's Solicitor |
 | Nicholas Rowe als Matinee "Sherlock Holmes" |
| Sam Coulson als Matinee "Thomas Kelmot" |
 | Hermione Corfield als Matinee "Ann Kelmot" |
 | Kit Connor als Boy |
 | Zoe Rainey als Boy's Mother |
 | Eileen Davies als Lady on Platform |
| Colin Starkey als Dr. John Watson |
 | Sarah Crowden als Mrs. Hudson |
| Elizabeth Jane Cassidy als Waitress (uncredited) |
| John Carr als Patron in Cinema (uncredited) |
 | Johnny Otto als Army Officer (uncredited) |
| Bill Condon | Director |
| Mitch Cullin | Novel |
| Jeffrey Hatcher | Screenplay |
| Arthur Conan Doyle | Characters |
| Carter Burwell | Original Music Composer |
| Tobias A. Schliessler | Director of Photography |
| Lucy Bevan | Casting |
| Virginia Katz | Editor |
| Martin Childs | Production Design |
| Keith Madden | Costume Design |
| Iain Canning | Producer |
| Anne Carey | Producer |
| Emile Sherman | Producer |
| Aviv Giladi | Executive Producer |
| Jonathan Houlding | Art Direction |
| James Wakefield | Art Direction |
| Charlotte Dirickx | Set Decoration |
| Susie Lewis | Costume Supervisor |
| Kim Armitage | Script Supervisor |
| Konnie Daniel | Key Hair Stylist |
| Dave Elsey | Makeup Designer |
| Jay Peck | Foley |
| Michael Minkler | Sound Re-Recording Mixer |
| Warren Shaw | Supervising Sound Editor |
| Renuka Ballal | Visual Effects Producer |
| John Bair | Visual Effects Supervisor |
| Sean Farrow | Visual Effects Supervisor |
| Marc Covington | Camera Operator |
| Karina Silva | Camera Operator |
| Jonathan Spencer | Gaffer |
| Jason Martin | Rigging Gaffer |
| Russell Kennedy | First Assistant Camera |
| Matt Windon | First Assistant Camera |
| Ko Iwagami | Casting |
| Emily Brockmann | Casting Associate |
| Ruth Key | Casting Associate |
| John Diesso | Digital Intermediate |
| Philippe Majdalani | Digital Intermediate |
| Daniel Triller | First Assistant Editor |
| Len Blavatnik | Executive Producer |
| Eliza Paley | Dialogue Editor |
| Eliza Paley | ADR Editor |
| Paul Carter | Property Master |
| Dave Elsey | Hair Designer |
| Greg Yolen | Co-Producer |
| Jack Morrissey | Co-Producer |
| Paul Ritchie | Co-Producer |
| Luca Borghese | Co-Producer |
| Christine Langan | Executive Producer |
| Zanne Devine | Executive Producer |
| Amy Nauiokas | Executive Producer |
| Vince Holden | Executive Producer |
| Kate Glover | Unit Production Manager |
| Lance Roehrig | First Assistant Director |
| Alexander Holt | Second Assistant Director |
| Dom Channing-Williams | Second Assistant Director |
