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.

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.

[6] He was replaced after two innings by Heinie Peitz, an actual catcher, but the Pirates had taken a 7–1 lead and went on to win the game.

[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.