Objective Personality affects an individual's ability to cope with the burden of chronic disease. However, the impact of personality on quality of life (QoL) in Parkinson's disease (PD) is not well characterized. The goal of this study is to determine the effect of personality on QoL in PD. Methods The study included 92 patients with idiopathic PD from Baltimore‐Washington area movement disorder neurology clinics. QoL was assessed using the 37‐item Parkinson's disease Quality of Life Questionnaire (PDQL) total score, and the Neuroticism–Extraversion–Openness Inventory was used to determine personality traits. Results Step‐wise regression models examined the contribution of personality, depression, demographic, and PD variables on PDQL‐assessed QoL. Neuroticism, conscientiousness, years of education, and depression explained 42% of the variance in the PDQL total score after adjusting for other disease variables. High neuroticism (β = −0.727, 95% confidence interval (CI) −1.125, −0.328, p < 0.0001) and depression (β = −9.058, 95%CI −17.46, −0.657, p = 0.035) negatively affected the PDQL, while high conscientiousness (β = 0.468, 95%CI 0.078, 0.858, p = 0.019), and years of education (β = 1.441, 95%CI 0.371, 2.510, p = 0.009) were positive factors. Conclusions Personality can have a positive or negative influence on QoL in PD. PD patients with otherwise similar disease burdens and depressive symptoms may experience different levels of QoL depending on the level of neurotic or conscientious personality traits. Therefore, when interpreting patient responses on the PDQL, it is important to understand whether they reflect aspects of PD, that is, motor impairment and depression, which are amenable to treatment or whether they reflect personality traits.