Road accidents are a major issue in Indonesia, and their number increases every year. Based on previous studies, mental fatigue is one of the biggest factors leading to road accidents and is majorly affected by mental workload. Driving duration is one of the factors that triggers mental fatigue. The prior literature cites electroencephalogram (EEG) measurement as the gold standard for measuring fatigue. However, there has been only limited study to examine the EEG indicators that are affected by driving duration, and the prior research still contains disagreements regarding the best EEG parameter for use in measuring fatigue. Therefore, this study aimed to evaluate the effect of driving duration on EEG fluctuation and determine the best EEG parameter related to fatigue. Seven participants were asked to spend three hours driving in a medium-fidelity simulator. A one-way ANOVA and correlation analysis were performed to measure the effect of driving duration on the EEG indicators and determine the correlation of the indicators. A Receiver Operating Characteristics (ROC) curve was also utilized to determine the variable with the greatest correlation with the subjective sleepiness indices. The results showed that at the end of three hours' driving, there was an increment in delta and theta activities, followed by a decrement in alpha and beta activities. In addition, the correlation of all bands was significant, with positive results for the alpha-beta and theta-delta bands, and a negative result in relation to each other. Furthermore, the results from the ROC curve revealed the Relative Power Ratio (RPR) of theta, the RPR of alpha, and the ratio of θ/α+β to be the best indicators among others, demonstrating a high degree of accuracy (above 85%).