In his book Before They Were Cardinals, John David Cash speculates that the two cities first competed in trade, which led to the creation of the St. Louis Brown Stockings in 1875 to compete with the Chicago White Stockings. This also led to the rivalry nickname ‘The Route 66 Series’, named for the road that connects both cities.
The first time these two teams met was in the 1885 World Series, playing in four cities—St. Louis, Chicago, New York, and Pittsburgh. The White Stockings (Cubs) beat the Browns (Cardinals) in games one and two, culminating in a Brown’s forfeiture over an umpire’s call in game two.