Attentional deficits have tragic consequences on road safety. These deficits are not solely caused by distraction, since they can also arise from other mental impairments such as, most frequently, mental fatigue. Fatigue is among the most prevalent impairing conditions while driving, degrading drivers’ cognitive and physical abilities. This issue is particularly relevant for professional drivers, who spend most of their time behind the wheel. While scientific literature already documented the behavioral effects of driving fatigue, most studies have focused on drivers under sleep deprivation or anyhow at severe fatigue degrees, since it is difficult to recognize the onset of fatigue. The present study employed an EEG-driven approach to detect early signs of fatigue in professional drivers during a simulated task, with the aim of studying visual attention as fatigue begins to set in. Short-range and long-range professional drivers were recruited to take part in a 45-min-long simulated driving experiment. Questionnaires were used to validate the experimental protocol. A previously validated EEG index, the MDrow, was adopted as the benchmark measure for identifying the “fatigued” spans. Results of the eye-tracking analysis showed that, when fatigued, professional drivers tended to focus on non-informative portions of the driving environment. This paper presents evidence that an EEG-driven approach can be used to detect the onset of fatigue while driving and to study the related visual attention patterns. It was found that the onset of fatigue did not differentially impact drivers depending on their professional activity (short- vs. long-range delivery).