The objective of the present study was to investigate the effects of multi-joint muscular fatigue on biomechanics of slips. Both lower-limb fatigue and upper-limb fatigue were examined, and the fatiguing exercises involved multi-joint movements to replicate muscular fatigue in realistic scenarios. Sixty healthy young adults participated in the study, and were evenly categorized into three groups: no fatigue, lower-limb fatigue, and upper-limb fatigue. These participants were instructed to walk on a linear walkway, and slips were induced unexpectedly during walking. The results showed that multi-joint muscular fatigue affects biomechanics of slips in all three phases of slips (i.e. initiation, detection, and recovery). In particular, adaptive safer postural control strategies were adopted with the application of both lower-limb fatigue and upper-limb fatigue to maintain the likelihood of slip initiation as in the no fatigue condition. In the phases of detection and recovery, lower-limb fatigue was found to compromise biomechanics of slips while upper-limb fatigue did not show any effects. Based on these findings, minimizing exposures to lower-limb fatigue should be given higher priority compared to upper-limb fatigue when developing interventions to prevent slip-induced falls. In addition, these findings also suggest that interventions aimed at enhancing proprioceptive acuity and increasing muscular strength in the lower limb could also be effective in slip-induced fall prevention.