The Cincinnati Reds’ 22-1 loss to the Philadelphia Phillies on Monday, July 6, is the worst defeat in the history of baseball’s oldest franchise. Going all the way back to 1869, no Reds team had lost a game by more than 20 runs before this debacle in Citizens Bank Park. Previous largest margin of defeat for the Reds since 1900 had been 19 runs on two occasions. Before 1900, they lost a game by 20 runs — to the Phillies.
| Margin | Date | Score | Opponent |
| 21 runs | July 6, 2009 | 22-1 | Philadelphia Phillies in Philadelphia |
| 20 runs | July 26, 1892 | 26-6 | Phillies in Philadelphia |
| 19 runs | Sept. 23, 1901 | 25-6 | Brooklyn Superbas in Cincinnati. |
| 19 runs | April 27, 1912 | 23-4 | Pittsburgh Pirates in Pittsburgh. |