Using a culturally-informed risk-protective framework, the purpose of this study was to examine spiritual well-being (existential, religious) as a moderator (protective factor) in the relation between neighborhood disorder (risk factor) and parenting stress in among a high risk sample of low-socioeconomic status (SES), African American women (N = 144). These women, who were primary caregivers of children aged between 8 and 12 reported on disorder in their existential and religious well-being, neighborhoods, and three types of parenting stress. Women who perceived more disorder in their neighborhood had more parenting stress, and women who reported more existential and religious well-being had less parenting stress. Existential (characterized by a sense of purpose in life), but not religious (characterized by a sense of life in relationship with God) well-being, moderated the relation between neighborhood disorder and all types of parenting stress such that women with medium or high levels of existential well-being had low levels of parenting stress at low levels of neighborhood disorder, but higher levels of parenting stress at higher levels of neighborhood disorder. No moderation effects were found at low levels of existential well-being. Results are framed in a context that emphasizes their relevance to incorporating family interventions that bolster culturally relevant resilience factors, such as spirituality, pertinent to low-SES African American families.