Neben Will Ferrell („Daddy's Home“-Reihe“, „Zoolander“-Reihe) und John C. Reilly („Kong Skull Island“, „Guardians of the Galaxy“) in den Hauptrollen ergänzen Ralph Fiennes („Heil: Cäsar!“, „James Bond: Spectre“), Rebecca Hall („Professor Marston and the Wonder Women“, „Iron Man 3“) sowie Rob Brydon („Swimming with the Men“) den prominenten Cast. Drehbuch und Regie hat Etan Cohen („Der Knastcoach“) übernommen. Produziert wurde HOLMES & WATSON von Will Ferrell, Adam McKay, Jimmy Miller und Clayton Townsend. Als Executive Producer zeichnen Chris Henchy, Jessica Elbaum und M. Riley verantwortlich.
Will Ferrell
Sherlock Holmes
John C. Reilly
Dr. John Watson
Rebecca Hall
Dr. Grace Hart
Ralph Fiennes
Prof. James Moriarty
Hugh Laurie
Mycroft Holmes
Kelly Macdonald
Mrs. Hudson
Steve Coogan
Gustav
Pam Ferris
Queen Victoria
Rob Brydon
Inspector Lestrade
Lauren Lapkus
Millie
Lilly Aspell
Urchin (uncredited)
Noah Jupe
Doxy
Bella Ramsey
Flotsam
Adam Scherr
Wrestler
Michael Culkin
Judge Over
Kieran O'Brien
PC Smalls
Jordan Long
Herbert
Jorge Leon Martinez
British Soldier
Billy Jenkins
Mudfog
Gerard Monaco
Officer
Scarlet Grace
Pickle
James Eeles
Manager Mr. Petrucka
Karl Farrer
Russian Merchant
Shawn Dixon
Upper Class Gentleman #1
Lindy Barrett
School Girl
Oliver Maltman
Telegraph Operator
Jason Thorpe
Butler
Martin Bassindale
One Man Band
Wolf Roth
Sigmund Freud
Mark Anthony Dawson
Beefeater #1
Ethan Rouse
Newsreader
Paddy Holland
Tough Kid
Willem Dalby
Newsie Man
Amelia O'Loughlin
White Star-Line Girl
Deepak Anand
Nobleman
Christian Wolf-La'Moy
English Gentleman
Sonnyboy Skelton
Doxy's Dad
Hector Bateman-Harden
Young Sherlock Holmes
Paul T.T. Easter
John
Daniel Fearn
The Drooling Man
Phil Hodges
Mr. Algernon Barkworth
Paul Cassidy
Charlie Chaplin
Anjan Kannan
Townsfolk
Laura Stevely
Sherlock's Mother
John Kinory
Instructing Solicitor
Joseph Macnab
Fitness Instructor
Russell Wilcox
The Announcer
Craig Thomas Lambert
Yeoman of the guard
Lochlan White
Newsie Kid - Timmy
Riley White
Newsie Kid - Jimmy
Benjamin Lok
Courtroom Person 3
Jamie Baughan
Titanic Captain
Sara Beasley
Mrs. Frobisher
Henrihs Ahmadejevs
Drunk
David Handley
Executioner
Martyn Mayger
Buckingham Palace Guest
Codie-Lei Eastick
Young Watson
Anthony Richard Rowe
Victorian Gentleman
Samantha Sharon Watson
Elizabeth - Lady of the Night
David Shackleton
Albert Einstein
Matthew Di Liello
Telly-Phone Assistant
David Stoller
Guard (Southampton)
Colby Mulgrew
Haybag
Darren Lake
Disorientated Man
Mick Slaney
Docker
Mark Behan
Ringside Bookie
Wesley Kent-Hargreaves
The Weird Child
David Bromley
Phone Guy
Ellie Rose Eames
Newschild
Joey Grima
Queen Victoria's Grenadier Guard
Angus Cook
Policeman
Neil Main
Screaming Soldier
Stanley Eldridge
Waiter 2
Edward Olhausen
Street Urchin
Nick Davison
Upper Class Gentleman (uncredited)
Hugh O'Brien
Garden Party Guest (uncredited)
Andrew G. Ogleby
Lower Class Citizen (uncredited)
Richard Price
Newsboy (uncredited)
Pete Freerunner Simpson
Police Officer (uncredited)
Bronson Webb
Jonathan Nightingale
Billy Zane
Himself
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