Michael York as Sherlock Holmes (voice)

Malcolm McDowell as Professor Moriarity (voice)

John Rhys-Davies as Dr. Watson (voice)

Billy West as Tom (voice)

Grey DeLisle as Red (voice)

Phil LaMarr as Spike / Policeman (voice)

Kath Soucie as Tuffy (voice)

Jeff Bergman as Butch / Droopy (voice)

Greg Ellis as Tin / Sergeant (voice)

Jess Harnell as Pan / Brett Jeremy (voice)

Richard McGonagle as Ali / First Policeman (voice)