Purpose: To examine the independent effect of single and multiple forms of substantiated childhood maltreatment (CM) on quality of life (QoL), controlling for selected potential confounders and/or covariates, and concurrent depressive symptoms. Methods: We used data from a prospective pre-birth cohort of 8556 mothers recruited consecutively during their first antenatal clinic visit at the Mater Hospital from 1981 to 1983 in Brisbane, Australia. The data were linked to substantiated cases of CM reported to the child protection government agency up to the age of 14 years. The sample consisted of 3730 (49.7% female) young adults for whom there were complete data on QoL at the 21-year follow-up. The mean age of participants was 20.6 years. Logistic regression models were used to assess the association between CM and QoL measured at the 21-year follow-up. Results: There were statistically significant associations between exposure to substantiated CM and poorer QoL. This also applied to the subcategories of childhood physical abuse, childhood emotional abuse (CEA), and neglect. These associations were generally stable after adjusting for confounders/covariates and concurrent depressive symptoms, except physical abuse. CEA with or without neglect significantly and particularly predicted worse subsequent QoL. Conclusions: Exposure to any substantiated maltreatment substantially contributed to worse QoL in young adulthood, with a particular association with CEA and neglect. Prior experiences of CM may have a substantial association with subsequent poorer QoL.