This study examines the association of cognitive functioning with urban neighborhood socioeconomic disadvantage and racial/ethnic segregation for a U.S. national sample of persons in late middle age, a time in the life course when cognitive deficits begin to emerge. The key hypothesis is that effects of neighborhood on cognitive functioning are not uniform but are most pronounced among subgroups of the population defined by socioeconomic status and race/ethnicity. Data are from the third wave of the Health and Retirement Survey for the birth cohort of 1931 to 1941, which was 55 to 65 years of age in 1996 (analytic N = 4,525), and the 1990 U.S. Census. Neighborhood socioeconomic disadvantage has an especially large negative impact on cognitive functioning among persons who are themselves poor, an instance of compound disadvantage. These findings have policy implications supporting "upstream" interventions to enhance cognitive functioning, especially among those most adversely affected by neighborhood socioeconomic disadvantage.