When a robbery takes place, Dr. Watson rushes to his colleague Sherlock Holmes and informs him about it. Holmes calls and asks Jerry to buy a copy of The Times.
When Tom chases Jerry, they end up in Holmes's apartment where Holmes was playing the violin for Dr. Watson during tea. Tom remembers the letter he was asked to deliver to Holmes. After reading it the letter sent by Red and her troubles, they decide to the theatre. Before Holmes leaves, he asks Tom and Jerry to cooperate with each other.
When the duo met the dancer Red who was being framed Holmes realise that it was a plot set up by his arch-nemesis - Professor Moriarty. He and Watson go looking for Moriarty after ordering Tom and Jerry to take Red to his apartment for her safety.
Moriarty activates his horseless carriage and he and Holmes fight atop the carriage. Tom accidentally breaks the brake and the carriage goes off on unfinished. Tom, Jerry, Red and Tuffy make it back. They believe Holmes to be dead. Dr. Watson arrives and finds Holmes holding on to the edge with the Crown Jewels.
He is last seen at Red's wedding with wolf.
- While Tom and Jerry: Willy Wonka and the Chocolate Factory is the first installment in the franchise to be directly based on another work of fiction, Holmes is one of the first characters in the franchise to be directly based on a literary character; the other two being Watson and Moriarty.