Fifty years after the passage of the Fair Housing Act, racial/ethnic residential segregation and discrimination persist in the housing market. In 2018, the National Fair Housing Alliance reported that the third and fifth largest discrimination complaints are made on the bases of familial status and sex, respectively. However, housing research has largely ignored how family structure may shape patterns of racial/ethnic residential segregation. By assessing residential isolation, our analyses add to the small body of literature exploring racial/ethnic segregation by family structure using data from the 1990–2010 decennial censuses and the 2006–2010 American Community Survey (ACS) drawn from the Neighborhood Change Database (NCDB) and the National Historical Geographic Information System (NHGIS). Our results reveal that white, married-couple families experience the greatest levels of residential isolation, net of controls for relevant socioeconomic and demographic factors. In addition, our within racial/ethnic group analyses indicate that black, female-headed families experience significantly more isolation than their married-couple counterparts, while the reverse is true for Hispanic and white families. Our results provide support for the tenets of the place stratification model and suggest researchers should consider family structure when assessing racial/ethnic residential segregation as race/ethnicity and family structure interact to shape housing outcomes in metropolitan America.