Led by first-year head coach Pop Warner, the Indians compiled a record of 9–2 and outscored opponents 383 to 46.

The 1899 Carlisle team drew further acclaim after defeating Columbia, 45–0, in a Thanksgiving Day game played at Manhattan Field near the Polo Grounds in New York.

[5] A press account of the game said: "The Indians were in prime physical condition and bore through the Columbia line and skirted the ends at will.

[6][7] The news reported the contest as the first matchup of East and West, but was pre-dated by the 1894 Chicago vs. Stanford football game.

At the end of the 1899 season, Seneca was elected as captain of the 1900 team, though he opted to play professional football rather than return in 1900.