Risky driving behaviors and the significant role of human factors in road accidents represent an important public health concern. This study investigated the relationship between neuroticism and neuropsychological functioning (frontal and temporal lobes, and basal ganglia) with risky driving behaviors among heavy vehicle drivers. A descriptive-correlational design was employed. The study population included truck-trailer and bus drivers attending driver health certificate service centers and vehicle inspection facilities in Najafabad (a city in Iran). Using cluster sampling, 100 participants were selected based on inclusion criteria. Data were collected through the Manchester Driving Behavior Questionnaire (DBQ), the NEO Five-Factor Inventory (NEO-FFI), and the Behavioral Inhibition/Activation Systems Questionnaire (BIS/BAS). Neuroticism was significantly and positively associated with risky driving behaviors (P < 0.05). Neuropsychological characteristics of the frontal and temporal lobes and basal ganglia showed strong correlations with risky driving, particularly in slips and errors. The correlation coefficient between personality traits and risky driving behaviors was r = 0.75, while the correlation with neuropsychological characteristics was r = 0.68. Preventive and intervention strategies aimed at modifying and improving driving behaviors are essential. Enhancing drivers’ personality and neuropsychological attributes may reduce risky driving and contribute to road safety.