Vickers started his career in organized professional baseball in 1900, when he played for the Toledo Mud Hens and the New Castle Quakers of the Interstate League.

[2] Cincinnati's last game of 1902 was scheduled for October 4 against the Pittsburgh Pirates, who had clinched the National League pennant.

In protest, Reds manager Joe Kelley submitted a lineup card with his players out of position, including Rube Vickers at catcher.

[4] Vickers caught two innings, during which he set the single-game modern-era MLB record for passed balls with six,[3]: 107 [5] a mark which has since been tied but not surpassed.

[2] While not playing for the Superbas in 1903, Vickers pitched for the Holyoke Paperweights of the Connecticut League, with whom he threw 287 innings and had a 22–10 win–loss record.

[1] However, he also played for a team that represented the independent Northern New York League in Burlington, Vermont,[9] which earned him the nickname "Kangaroo" (for what fans considered "contract jumping").

[1] Vickers played the entire 1906 season with the Siwashes, during which he set several Pacific Coast League records.

[2][18]: 25 After the 1909 season, Athletics manager Connie Mack sent Vickers to the Baltimore Orioles of the Eastern League.