He was a football coach at Everett High School (1909–1915), Purdue University (1916–1917), Holy Cross (1919–1930) and Saint Anselm College (1935–1940).

In the final game of the 1906 season, played at the Polo Grounds, O'Donnell scored both of Holy Cross's touchdowns in a 15–6 win over Fordham.

The Times wrote: Again and again by the sheer force of his phenomenal running O'Donnell took the ball through the Fordham line and gained a dozen first downs.

In fact, not once during the whole progress of the game was the remarkable back stopped for a loss, but, unsupported as he was, the herculean task of beating a well-drilled eleven was too much for him.

... Several stretches of thirty yards were made by his rushing, but eventually Holy Cross was forced to kick, and their advances ended there.

[7] The Boston Evening Transcript wrote at the time, "Since Cleo O'Donnell took charge of the Suburban League school's athletics, he has had remarkable success, but this year's team is his masterpiece.

[10] In August 1919 he returned his alma mater as the graduate manager of athletics and head football coach of the Holy Cross Crusaders.

[12] In early 1930, O'Donnell stepped down as head football coach at Holy Cross, but remained at the school as athletic director until December 1933.

[16] In April 1935, O'Donnell was hired as the head football coach and athletic director at Saint Anselm College in Goffstown, New Hampshire.

[25] On February 14, 1953, O'Donnell collapsed and died suddenly while attending a testimonial dinner for his former pupil, Harry McMahon, at Southbridge, Massachusetts.