Significance The biological changes associated with cognitive decline in aging are complex. Age-related changes in the striatum have been hypothesized as potentially important for predicting declining memory function over the adult life span, but empirical support for this hypothesis is sparse. We provide evidence from human fMRI and PET data for the association of age-related differences in striatal function to memory decline. A reduction of specificity (i.e., dedifferentiation) in functional coupling between the caudate and regions of the default network predicted memory decline over subsequent years in older adults. An age-related reduction in density of presynaptic striatal dopamine transporters also predicted memory decline but was unrelated to functional dedifferentiation, suggesting that relations between age-related changes in striatal functions and memory are multifaceted.