The purpose of this study is to evaluate if locus of control (LOC) predicts various quality of life (QOL) and mental well-being measures among terminally ill cancer patients at the time of palliative care consult. Multi-site analysis of patients with advanced cancer being seen as new patients in a Palliative and Supportive Care outpatient clinic. Patients completed the following surveys: locus of control (LOC) scale, Functional Assessment of Chronic Illness Therapy-General (FACT-G), Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), Hospital Anxiety Depression Scale (HADS), and Herth Hope Index (HHI). Regression models were created to examine the effect of LOC upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of age, gender, race, partnership status, education, and months since diagnosis as potential confounders. This study enrolled 100 patients. After adjusting for site, race, and partnership status, higher levels of LOC chance predicted decreased QOL (FACT-G) (p < 0.01). Higher levels of LOC chance also correlated with increased depression and anxiety (p < 0.01) and decreased meaning/peace and faith (p < 0.01). Additionally, higher levels of LOC chance predicted decreased hope (HHI) (p < 0.001). Terminally ill cancer patients with a high LOC chance may be at risk for decreased physical and mental well-being at the end of life. Efforts should be made to identify these patients and design interventions to increase their feeling of control over the situation in order to improve physical and mental well-being at the end of life.