Background: Despite the growing attention surrounding crack cocaine use in Brazil, little is understood about crack users’ histories, use patterns and the interplay of drug-use behaviors, settings, and access/barriers to care. Qualitative studies seldom cross-compare findings regarding people who use crack from different settings. This study aims to explore the insights of regular crack users in two major Brazilian cities and to examine how social and contextual factors, including stigma and marginalization, influence initial use and a range of health and social issues. Methods: In-depth interviews and focus groups were conducted with 38 adult crack cocaine users recruited from impoverished neighborhoods in Rio de Janeiro and São Paulo. Interviews and focus groups were audio recorded and transcribed verbatim. Qualitative analysis was carried out, and content was organized and analyzed by recurrent themes relevant to study interests. Results: For study participants from both cities, frequent crack cocaine use plays a central role in daily life and leads to a range of physical, psychological, and social consequences. Common concerns among users include excessive crack use, engagement in risky habits, infrequent health service utilization, marginalization, and difficulty reducing use. Conclusions: Disadvantaged conditions in which many crack cocaine users grow up and live may perpetuate risk behaviors and stigma may further marginalize users from necessary health and recovery services. Reducing stigma and moralizing discourse related to drug use, especially among health professionals and law enforcement personnel, may help encourage users to seek necessary care. New harm-reduction-based care and treatment alternatives for marginalized drug users are being developed in parts of Brazil and elsewhere and should be adapted and expanded for other populations in need.