A single molecule of H₂O without any hydrogen bonds is completely isolated within the confined sub-nano space inside fullerene C₆₀.  With the concept of dynamic control of opening size, an open-cage C₆₀ derivative was synthesized, whose opening can be enlarged in situ at 120 ºC resulting in quantitative encapsulation of a molecule of H₂O under the high-pressure conditions.  The easy method to restore the opening was developed to realize the organic synthesis of water-encapsulating C₆₀.  The structure of H₂O@C₆₀ was clearly determined by the single crystal X-ray analysis, and the properties of the single H₂O molecule as well as the spherical π-system encapsulating the water molecule were studied.