Mental health comorbidities among individuals with a substance use disorder are common. This study provides an analysis of the prevalence, risk factors, and treatment outcomes (depression, anxiety and stress, and cravings) of individuals with comorbid depression, anxiety, posttraumatic stress disorder (PTSD), obsessive compulsive disorders (OCD), and/or eating disorders attending residential substance use treatment centers. Intake and three-month post-discharge assessments of 603 (69.3% men) people attending residential substance use treatment services were conducted using the Mental Health Screening Scale, Addiction Severity Index, Depression, Anxiety Stress Scale, and a cravings measure. Anxiety disorders were common (94.5%), followed by depression (89.6%), PTSD (62.0%), OCD (33.7%), and eating disorders (21.4%). Nearly a quarter reported two comorbidities and 8.5% reported five comorbidities. Higher comorbidity levels were associated with having poorer mental health but not cravings at three-month post-discharge follow-up. Comorbidity is common and complex in presentations to residential substance use treatment settings. Higher levels of comorbidity are linked to poorer mental health, which remains over time.