Both Subjective Cognitive Decline (SCD) and mental fatigue are becoming increasingly prevalent as global demographics shifts indicate our aging populations. SCD is a reversible precursor for Alzheimer’s disease, and early identification is important for effective intervention strategies. We aim to investigate the association between mental fatigue—as well as other factors—and SCD. A total of 707 old adults (aged from 60 to 99) from Shanghai, China, participated in this study and completed self-reported instruments covering their cognitive and mental status as well as demographic information. Mental fatigue status was assessed by using four items derived from the functional impairment syndrome of the Old Adult Self Report (OASR). SCD was assessed by using the Memory/Cognition syndrome of OASR. A total of 681 old adults were included in the current study. The means of SCD significantly differed between each group of factors (age, gender, and mental fatigue). The general linear regression models showed that SCD increased with age, females scored higher than males, and SCD was positively associated with mental fatigue factors including difficulty getting things done, poor task performance, sleeping more, and a lack of energy among old adults. The study also found that SCD is negatively associated with the high-income group among young-old (aged from 60 to 75) males and associated with good marital/living status with the companion of spouses/partners among young-old females. These results suggest that gender, income level, marital/living status, and mental fatigue are crucial factors in preventing SCD among old adults and are pivotal in developing early intervention strategies to preserve the mental health of an increasingly aging population.