He is voiced by Alfred Molina, who also played Doctor Octopus in Spider-Man 2, Satipo in Raiders of the Lost Ark, Johann Tetzel in Luther, Ke-Pa in Kung Fu Panda: Legends of Awesomeness, Mr. Freeze in Harley Quinn, Reverend Leland Drury in White Fang 2: Myth of the White Wolf, Maxim Horvath in The Sorcerer's Apprentice, Lasombra in Hey Arnold! and The Duke in Solar Opposites.
On a climbing expedition in the Himalayas, Professor Jeffries is led by his Sherpa, Pemba, to a high point on a mountain using an ancient tablet. Jeffries is out looking for the Abominable Snowman, who lives in the mountains. He's convinced that the Snowman lives close by, but Pemba tells him he won't lead Jeffries anymore, as it would be intruding on the territory of the Abominable Snowman.
Jeffries, who seems to care about the Snowman over their safety, decides to cut the rope and continue. Later he is seen with Pemba in the village. The two of them return to the mountain along with Scooby-Doo, Shaggy Rogers and Alphonse LaFleur, who just arrived. During the night, Jeffries disappears. Much later in the film, he is finally seen again stealing the scared crystals. Scooby, Shaggy, Pemba and the rest of Mystery Inc. catch him in a net only to be attacked by the Abominable Snowman. Jeffries frees himself from the net and escapes the cave.
He is later caught in climbing ropes and thrown in jail for his crimes.