Ittihad lost patience with the 49-year-old following the team's 2-1 home defeat by Al Nasr at the weekend, according to the AFC's website.
Calderon had been under pressure since Ittihad were beaten 2-1 by South Korea's Pohang Steelers in the final of the Asian Champions League final last November.
Ittihad said they will appoint Hassan Khalifa as cartaker coach while they search for a new manager.
Saudi Arabia's top club are currently third in the domestic league standings with 29 points from 15 matches. Al Hilal are top with 41 points.
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