Objective: In Mexico, specialized treatment services for people with co-occurring disorders are limited within public health services, while private options are deemed too costly. More than 2,000 community-based residential care facilities have risen as an alternative and are the main source of treatment for individuals with substance use disorders; however, suboptimal practices within such facilities are common. Information on the clinical characteristics of patients receiving care in these facilities is scarce and capacity to provide high-quality care for co-occurring disorders is unknown. The aims of this study were to examine the prevalence of co-occurring disorders in patients receiving treatment for substance use in these community-based residential centers and to assess whether the presence of co-occurring disorders is associated with higher severity of substance use, psychiatric symptomatology, and other health risks. Methods: This study was conducted with 601 patients receiving treatment for substance use disorders at 30 facilities located in five Mexican states, recruited in 2013 and 2014. Patients were assessed with self-report measures on substance use, service utilization, suicidality, HIV risk behaviors, psychiatric symptomatology, and psychiatric disorder diagnostic criteria. Results: The prevalence of any co-occurring disorder in this sample was 62.6%. Antisocial personality disorder was the most prevalent (43.8%), followed by major depressive disorder (30.9%). The presence of a co-occurring disorder was associated with higher severity of psychiatric symptoms (aB = .496, SE = .050, p < .05); more days of substance use (aB = .219, SE = .019, p < .05); current suicidal ideation (aOR = 5.07, 95% CI [2.58, 11.17]; p < .05), plans (aOR = 5.17 95% CI [2.44, 12.73]; p < .05), and attempts (aOR = 6.43 95% CI [1.83, 40.78]; p < .05); more sexual risk behaviors; and more contact with professional services (aOR = 1.77, 95% CI [1.26, 2.49], p < .05). Conclusions: Co-occurring disorders are highly prevalent in community-based residential centers in Mexico and are associated with significantly increased probability of other health risks. This highlights the need to develop care standards for this population and the importance of clinical research in these settings.