Gravity has long been purported to serve a unique role in sensorimotor coordination, but the specific mechanisms underlying gravity-based visuomotor realignment remain elusive. In this study, astronauts (nine males, two females) performed targeted hand movements with eyes open or closed, both on the ground and in weightlessness. Measurements revealed systematic drift in hand-path orientation seen only when eyes were closed and only in very specific conditions with respect to gravity. In weightlessness, drift in path orientation was observed in two postures (seated, supine) for two different movement axes (longitudinal, sagittal); on Earth, such drift was only observed during longitudinal (horizontal) movements performed in the supine posture. In addition to providing clear evidence that gravitational cues play a fundamental role in sensorimotor coordination, these unique observations lead us to propose an “inverted pendulum” hypothesis to explain the saliency of the gravity vector for eye–hand coordination—and why eye–hand coordination is altered during body tilt or in weightlessness.