The whimsical drawing of a cigar-chomping man with a derby hat was made around 1920 before Disney hit it big in the entertainment world.
The drawing, estimated to be worth $35,000 to $50,000, will be among 1,400 items up for sale at the two-day auction set to begin Tuesday at the Atlantis Casino Resort.
The auction will be staged by Holabird-Kagin Americana.
Company spokesman Fred Holabird says pieces signed by Disney are rare, and the drawing is one of his earliest signed pieces, if not the earliest. Disney was around 20 years old when he drew it.
Also up for auction is a unique California Gold Rush coin expected to fetch up to $175,000.