The prevalence of obesity in older adults, particularly in females, is increasing rapidly and is associated with declines in both the brain and physical health. Both the obese and the female populations have shown greater motor fatigue than their counterparts, however, the central neural mechanisms for fatigue are unclear. The present study measured fatigue-related functional connectivity across frontal and sensorimotor areas using functional near-infrared spectroscopy (fNIRS). Fifty-nine older adults (30 non-obese and 29 obese) performed submaximal handgrip motor fatigue until voluntary exhaustion. Functional connectivity and cerebral hemodynamics were compared across eight cortical areas during motor fatigue and across obesity and sex groups along with neuromuscular fatigue outcomes (i.e., endurance time, strength loss, and force steadiness). Both obesity- and sex-specific functional architecture and mean activation differences during motor fatigue in older adults were observed, which were accompanied by fatigue-related changes in variability of force steadiness that differed between groups. While primary indicators of fatigue, i.e., endurance and strength loss, did not differ between groups, the motor steadiness changes indicated different neural adaptation strategies between the groups. These findings indicate that obesity and sex differences exist in brain function in older adults, which may affect performance during motor fatigue.