Space agencies are planning to send humans back to the Lunar surface, in preparation for crewed exploration of Mars. However, the effect of hypogravity on human skeletal muscle is largely unknown. A recently established rodent partial weight-bearing model has been employed to mimic various levels of hypogravity loading and may provide valuable insights to better understanding how human muscle might respond to this environment. The aim of this study was to perform a systematic review regarding the effects of partial weight-bearing on the morphology and function of rodent skeletal muscle. Five online databases were searched with the following inclusion criteria: population (rodents), intervention (partial weight-bearing for ≥1 week), control (full weight-bearing), outcome(s) (skeletal muscle morphology/function), and study design (animal intervention). Of the 2,993 studies identified, eight were included. Partial weight-bearing at 20%, 40%, and 70% of full loading caused rapid deconditioning of skeletal muscle morphology and function within the first one to two weeks of exposure. Calf circumference, hindlimb wet muscle mass, myofiber cross-sectional area, front/rear paw grip force, and nerve-stimulated plantarflexion force were reduced typically by medium to very large effects. Higher levels of partial weight-bearing often attenuated deconditioning but failed to entirely prevent it. Species and sex mediated the deconditioning response. Risk of bias was low/unclear for most studies. These findings suggest that there is insufficient stimulus to mitigate muscular deconditioning in hypogravity settings highlighting the need to develop countermeasures for maintaining astronaut/cosmonaut muscular health on the Moon and Mars.