The chronic exposure of astronauts to microgravity results in structural degradation of their lower limb bones. Currently, no effective exercise countermeasure exists. On Earth, the impact loading that occurs with regular locomotion is associated with the maintenance of bone's structural integrity, but impact loads are rarely experienced in space. Accurately mimicking Earth-like impact loads in a reduced-gravity environment should help to reduce the degradation of bone caused by weightlessness. We previously showed that running with externally applied horizontal forces (AHF) in the anterior direction qualitatively simulates the high-impact loading associated with downhill running on Earth. We hypothesized that running with AHF at simulated reduced gravity would produce impact loads equal to or greater than values experienced during normal running at Earth gravity. With an AHF of 20% of gravity-specific body weight at all gravity levels, impact force peaks increased 74%, average impact loading rates increased 46%, and maximum impact loading rates increased 89% compared to running without any AHF. In contrast, AHF did not substantially affect active force peaks. Duty factor and stride frequency decreased modestly with AHF at all gravity levels. We found that running with an AHF in simulated reduced gravity produced impact loads equal to or greater than those experienced at Earth gravity. An appropriate AHF could easily augment existing partial gravity treadmill running exercise countermeasures used during spaceflight and help prevent musculoskeletal degradation.