Down's syndrome is most commonly caused by:

Most common cause of Down syndrome (trisomy) is meiotic nondisjunction. Since maternal age is a significant factor for the incidence of Down's, it also suggests that in most cases the nondisjunction takes place in the ovum (Maternal Nondisjunction). Ref: Robbin's Basic Pathology, 7th Edition, Page 230; Essentials of Human Disease By Leonard Crowley, Page 112.