Yerkes was born into a Quaker family in the Northern Liberties, a district adjacent to Philadelphia, on June 25, 1837. His mother Elizabeth Link Yerkes died of puerperal fever when he was five years old and shortly thereafter his father Charles Tyson Yerkes Sr. was expelled from the Society of Friends for marrying a non-Quaker. After finishing a two-year course at Philadelphia's Central High School, Yerkes began his business career at the age of 17 as a clerk in a local grain brokerage. In 1859, aged 22, he opened his own brokerage firm and joined the Philadelphia stock exchange.