A native of Charlestown, Massachusetts, O'Donnell attended the Boston Latin School before enrolling at the College of Holy Cross in 1904. He played four years for the Holy Cross Crusaders football team. He was a tackle in the 1904 and 1905 seasons, and end in 1906, and a fullback in 1907. In the final game of the 1906 season, played at the Polo Grounds, O'Donnell scored both of Holy Cross's touchdowns in 15–6 win over Fordham. He was selected by his teammates as captain of the 1907 team. His final game for Holy Cross was a 34–0 loss to Fordham. Despite the one-sided game, The New York Times singled out "O'Donnell's Pretty Play" as the feature of the contest. The Times wrote: