Cognitive reserve is increasingly recognized as an important determinant of resilience against cognitive decline. In this cross-sectional study of 250 Brazilian older adults, higher cognitive reserve, particularly leisure-time engagement and years of education, as well as favorable physical resilience-related factors—including physical activity, handgrip strength, gait speed, and calf circumference—were associated with lower odds of cognitive decline. Conversely, frailty and alcohol consumption were associated with higher odds. These findings support multidomain approaches to promote healthy cognitive aging in older adults from middle-income countries.