Parenting a child with Down syndrome may pose unique challenges for parents’ relationship quality. This study used structural equation modeling with a sample of 351 mothers of children with Down syndrome to test if hope mediated the association between mothers’ various coping behaviors and mothers’ relationship quality. Hope was defined as a generalized positive state that comes from a personal sense of agency. Results indicated a greater degree of religious coping and internal coping were each significantly associated with more hope, whereas support seeking was not related with more hope. Higher hope was significantly associated with greater relationship quality. Bootstrapped indirect effects from both religious coping and internal coping to hope, and then hope to relationship quality, were identified. Implications for therapists and future research are described.