He played ten seasons in Major League Baseball (MLB) between 1898 and 1907 for the Washington Senators, Brooklyn Superbas, Detroit Tigers, and Chicago Cubs.

[3] Casey reportedly earned the nickname "Doc" because he sometimes used his knowledge of dentistry to assist fellow baseball players with their teeth.

He appeared in 28 games for the Senators in 1898, principally as a third baseman, and compiled a .277 batting average with 15 stolen bases.

[9] Casey appeared in 143 games and stole 27 bases and helped lead the 1899 Brooklyn club to the National League championship and a 101–47 record.

[6] In May 1900, Sporting Life reported that Casey had been "loaned" by the Brooklyn club to the Detroit Tigers of the newly formed American League.

Sporting Life reported on the reaction to Casey's departure: "Brooklyn cranks will be sorry to see the little fellow depart, for he came to this city when the club was in a bad way, and did a great deal to bring the championship to the nine, when it looked for a time as if it might not be won because of the injuries to players.

During Casey's three years with the Cubs, he was the fourth member of the infield that included Tinker to Evers to Chance.

[6] He also had the seventh highest defensive Wins Above Replacement rating among all position players – higher even than Evers and Chance.

He also compiled a career high 176 putouts at third base in 1907 – the third highest total by any National League third baseman that year.

[3] In November 1910, Casey was hired by Claud H. Varnell, owner of the Fort Wayne, Indiana baseball club (Central League) to serve as manager for the 1911 season.

Casey's drug store reportedly "became known to thousands of fans as headquarters of the city's Winter Stove League.