The purpose of this study was to investigate the association of intimate partner victimization experiences, mental health (MH), and substance misuse problems with the risk for lethality among women of African descent. Data for this cross-sectional study were derived from a large case-control study examining the relationship between abuse status and health consequences. Women were recruited from primary care, prenatal, or family planning clinics in Baltimore and the U.S. Virgin Islands. Logistic regression was used to generate the study findings. Among 543 abused women, physical and psychological abuse by intimate partners, comorbid posttraumatic stress disorder (PTSD) and depression symptoms, and PTSD-only problems significantly increased the likelihood of lethality risk. However, victims’ substance misuse and depression-only problems were not associated with the risk for lethality. In addition, PTSD symptoms mediated the relationship between severe victimization experiences and risk for lethality. Practitioners should pay attention to victimization experiences and MH issues when developing treatment and safety plans. Policies to fund integrated services for African American and African Caribbean women with victimization and related MH issues, and training of providers to identify at-risk women may help reduce the risk for lethality in intimate partner relationships.