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| Basil Rathbone | Sherlock Holmes |
| Nigel Bruce | Dr. John H. Watson |
| Lionel Atwill | Prof. Moriarty |
| Karen Verne | Charlotte Eberli |
| William Post Jr. | Dr. Franz Tobel |
| Dennis Hoey | Inspector Lestrade |
| Mary Gordon | Mrs. Hudson |
| Holmes Herbert | Sir Reginald Bailey |
| Henry Victor | Professor Frederick Hoffner (uncredited) |
| Paul Fix | Mueller (uncredited) |
| Rudolph Anders | Braun (uncredited) |
| Harold De Becker | Peg Leg (uncredited) |
| Harry Cording | Jack Brady (uncredited) |
| Harry M. Woods | Kurt (uncredited) |
| George Burr Macannan | Gottfried (uncredited) |
| Paul Bryar | Swiss waiter (uncredited) |
| Vicki Campbell | Female RAF pilot (uncredited) |
| Guy Kingsford | Foot patrolman (uncredited) |
| James Craven | RAF officer watching bombsight test (uncredited) |
| George Eldredge | Policeman outside Durer's (uncredited) |
| Michael Mark | George (uncredited) |
Sherlock Holmes saves noted Swiss physicist Franz Tobel from the Gestapo in Zurich and smuggles him to London. There, Tobel is reunited with his wife, Charlotte, to whom he gives a coded message in the event he disappears. Tobel presents the weapon he developed to government officials, and when he is subsequently abducted by arch-villain Professor Moriarty, Holmes and Dr. Watson risk their lives to find him.
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