The most scholarly commissioner, Giamatti was a lifelong Red Sox fan (having grown up in Boston) with a tremendous passion for the game. Serving ten years as president of Yale, he left that position to joined Major League Baseball as the president of the National League in 1986. Giamatti worked hard to preserve baseball's traditions, and he campaigned heavily to improve the fan atmosphere at the ballpark.

After becoming Commissioner, he appointed Fay Vincent as his deputy. Deeply concerned about preserving baseball's integrity, he undertook a lengthy investigation and litigation regarding baseball's all time hit leader Pete Rose and gambling. On August 23, 1989, Rose reached agreement with Giamatti, which translated into a lifetime suspension from the game. It is often said that the whole Rose affair broke Giamatti's heart; as he died shortly after on September 1, 1989 from a heart attack.