Problems with memory, executive function, and language are a significant public health concern, especially when they begin during midlife. However, there is relatively little work on risk and protective factors for cognitive function in middle adulthood. Using data from 883 Mexican-origin adults assessed up to 6 times across 12 years (Meanage at Time 1 = 38.2 years; range = 27 to 63 years), the present study examined whether developmental trajectories (levels and slopes) of Big Five personality domains and socioeconomic factors (per capita income, economic stress) were prospectively associated with cognitive function (memory, mental status, verbal fluency) at the final assessment. We found that individuals with higher levels of, and smaller decreases in, Neuroticism had worse cognitive function 12 years later. Further, individuals with higher initial Conscientiousness had better subsequent memory, mental status, and verbal fluency, and individuals with higher Openness and Extraversion had better subsequent verbal fluency (but not memory or mental status). The trajectories of per capita income and economic stress were robustly associated with cognitive function, such that higher initial levels and greater increases in socioeconomic resources had protective associations, whereas higher levels and greater increases in economic stress had deleterious associations with cognitive function. Higher education level was associated with better cognitive function 12 years later. These findings suggest that changes in personality and socioeconomic factors across adulthood are associated with cognitive function, which may be informative for interventions to support healthier cognitive aging starting at least as early as midlife.