People seeking treatment for substance use disorders (SUD) ultimately aspire to improve their quality of life (QOL) through reducing or ceasing their substance use, however the association between these treatment outcomes has received scant research attention. In a prospective, multi-site treatment outcome study (‘Patient Pathways’), we recruited 796 clients within one month of intake from 21 publicly funded addiction treatment services in two Australian states, 555 (70%) of whom were followed-up 12 months later. We measured QOL at baseline and follow-up using the WHOQOL-BREF (physical, psychological, social and environmental domains) and determined rates of “SUD treatment success” (past-month abstinence or a statistically reliable reduction in substance use) at follow-up. Mixed effects linear regression analyses indicated that people who achieved SUD treatment success also achieved significantly greater improvements in QOL, relative to treatment non-responders (all four domains p < 0.001). Paired t-tests indicated that non-responders significantly improved their social (p = 0.007) and environmental (p = 0.033) QOL; however, their psychological (p = 0.088) and physical (p = 0.841) QOL did not significantly improve. The findings indicate that following treatment, QOL improved in at least some domains, but that reduced substance use was associated with both stronger and broader improvements in QOL. Addressing physical and psychological co-morbidities during treatment may facilitate reductions in substance use.