Carlisle played games against college football's "Big Four" (Harvard, Yale, Princeton, and Penn) and nearly defeated Yale. The New York Times reported on a run by Isaac Seneca that nearly won the game against Yale:
"Seneca was given the ball to go through the centre. He got through with one or two Yale men hanging on to him. Then he squirmed and shook off the Yale men, dodged a man or two, and, making a splendid run down the field, made what was thought to be a touchdown. Nearly all on the grounds shouted themselves hoarse. Men waved their hats in the air, pretty gals clapped their hands ..."
However, the referee waved off the touchdown, ruling that Seneca was "down" when the Yale players hung on to him. The New York Times wrote the next day that the referee had made the wrong call and that Carlisle had been robbed of a touchdown, but the game went into the record books as a 12–6 win for Yale.