The Tigers promoted Granderson to the MLB for the first time in September 2004. He made his MLB debut on September 13 against the Minnesota Twins. He received his second promotion to the majors in July 2005, and he appeared in six games. After his third promotion to the MLB, in August, he remained in the majors permanently. Granderson had his first career MLB inside-the-park home run on September 15, a five-hit game September 18 and a walk-off home run on September 26 against the Chicago White Sox.