After graduating from Rush, Anderson took a job as head football coach at the College of the Holy Cross in Massachusetts.

During that time, Anderson also served as the head of eye, ear, nose, and throat clinic at Boston's Veterans Hospital.

Iowa had a record of just 2–13–1 in 1937 and 1938 under Irl Tubbs, and the Hawkeyes had finished among the worst three teams in the Big Ten Conference standings every year in the 1930s except 1933.

Iowa had won just one conference game in the last three years, and the team they beat, Chicago, announced that they would be dropping their football program following the 1939 season.

Before the first game, The Des Moines Register had a small note stating that "a set of iron men may be developed to play football for Iowa.

Jim Gallager of the Chicago Herald-American wrote, "It's doubtful if any coach in football history ever accomplished such an amazing renaissance as Eddie Anderson has worked at Iowa.

He was also given a significant share of stock in Amana Refrigeration by the founder and CEO of the company, George Foersner, as a reward for his coaching that season.

After that season, Anderson took a leave of absence to serve in the U.S. Army Medical Corps during World War II.

Iowa left the football program in the hands of interim coaches Slip Madigan and Clem Crowe while Anderson was gone from 1943 to 1945.

"[4] Anderson used his larger coaching staff to hire Leonard Raffensperger as the head of the freshman team.

After resigning at Holy Cross in 1964, Anderson was named the chief of outpatient services at the Veterans Administration Medical Center in Rutland, Massachusetts.

Anderson gave the acceptance speech for that year's class at the College Football Hall of Fame.

He summarized his coaching philosophy when he said, "The victory most savored and cherished is the one that didn't come about by beating the rules, but by playing within them, where defeat is only a condition of the moment.