This study investigated how music tempo impacted drivers’ fatigue and quality of attention in a long-distance monotonous highway environment. Sixteen drivers were enrolled in four sessions of real-road driving tests under the following four music conditions: no music, slow tempo, medium tempo and fast tempo. Specifically, the drivers’ electroencephalogram parameters and eye movement parameters were recorded to measure their extent of fatigue and quality of attention, respectively. Of the three tempos, medium-tempo music is the best choice to reduce fatigue and maintain attention for a long-distance driving. Slow-tempo music can temporarily boost the quality of attention, but after a long period of driving, it significantly deteriorates the driver’s levels of fatigue and attention. Fast-tempo music helps relieve driver fatigue but significantly deteriorates drivers’ attention after an extended driving time. This study offered practical references for drivers regarding the use of music to avoid fatigue, maintain attention and improve their driving safety. Based on previous theories of music and driving, we have explored the underlying mechanism of how music tempo maintains the alertness of drivers.