Lay health advisor (LHA) programs have made strong contributions towards the elimination of health disparities and are increasingly being implemented to promote health and prevent disease. Developed in collaboration with African-American survivors, the National Witness Project (NWP) is an evidence-based, community-led LHA program that improves cancer screening among African-American women. NWP has been successfully disseminated, replicated, and implemented nationally in over 40 sites in 22 states in diverse community settings, reaching over 15,000 women annually. We sought to advance understanding of barriers and facilitators to the long-term implementation and sustainability of LHA programs in community settings from the viewpoint of the LHAs, as well as the broader impact of the program on African-American communities and LHAs. In the context of a mixed-methods study, in-depth telephone interviews were conducted among 76 African-American LHAs at eight NWP sites at baseline and 12-18 months later, between 2010 and 2013. Qualitative data provides insight into inner and outer contextual factors (e.g., community partnerships, site leadership, funding), implementation processes (e.g., training), as well as characteristics of the intervention (e.g., perceived need and fit in African-American community) and LHAs (e.g., motivations, burnout) that are perceived to impact the continued implementation and sustainability of NWP. Factors at the contextual levels and related to motivations of LHAs are critical to the sustainability of LHA programs. We discuss how findings are used to inform (1) the development of the LHA Sustainability Framework and (2) strategies to support the continued implementation and sustainability of evidence-based LHA interventions in community settings.