The aim of this study was to investigate the development of back muscle activity during a simulated 4.5-h truck drive with professional long-haul truck drivers and to assess the effects of a seat-integrated stimulation on muscle activity during the drive. Muscle activity was compared intra-individually between a stimulation condition (with seat-integrated stimulation) and a no-stimulation condition (without seat-integrated stimulation) in a simulated driving study (N = 16). During the drive, sEMGs of the m. trapezius pars descendens, m. trapezius pars ascendens and m. erector spinae were recorded bilaterally and the RMS values of the sEMG amplitudes were analyzed. There was a significant increase in muscle activity within 1-h driving periods (in m. trapezius pars descendens and m. trapezius pars ascendens) in both the stimulation and the no-stimulation condition but not within the whole sitting duration (in all muscles). Contrary to our expectations, the RMS values did not differ between conditions. Short-term effects on back muscle activity of long-haul truck drivers during 1-h driving periods were found with and without the seat-integrated stimulation. However, interruptions of the driving task seemed to be sufficient to eliminate these effects. These findings on back muscle activity in long-haul drivers reveal new insights as to what affects the musculoskeletal system in prolonged driving. In future studies, an uninterrupted driving task under real conditions should be used to investigate possible effects of prolonged driving on truck drivers' muscle activity in general and of seat-integrated stimulation on back muscle activity in particular.