Yerkes moved to Chicago from his native Philadelphia in 1881 after making a fortune for himself handling the sale of municipal bonds. He spent some time in jail following economic losses tied to the Great Chicago Fire which meant he was unable to pay off his creditors. This event in Yerkes's life, as well as his future successes would form the bases for the Theodore Dreiser novels, The Financier, The Titan and The Stoic, in which Yerkes was fictionalized as Frank Cowperwood.
Yerkes turned his attention to building and improving the Chicago public transportation system through the use of graft. A partially reformed City Council under Mayor Carter Harrison, Jr fought against Yerkes, with the swing votes coming from aldermen "Hinky Dink" Kenna and "Bathhouse" John Coughlin. In an attempt to reform his image, Yerkes renovated a couple of tunnels under the Chicago River and built two bridges over the river. He also contributed nearly $300,000 to the University of Chicago to establish Yerkes Observatory in Williams Bay, Wisconsin.
Following his time in Chicago, Yerkes moved to London where he used his experience to help build much of that city's tube system, the London Underground.