During a driving task, the seat-driver interface is particularly influenced by the external environment and seat features. This study compares the effect of two different seats (S-1 - soft & S-2 - firm) and the effect of visual simulation of different road types (city, highway, mountain, country), on pressure distribution and perceived discomfort during prolonged driving. Twenty participants drove two 3-h sessions (one per seat) on a static simulator. Contact Pressure (CP), Contact Surface (CS), and Seat Pressure Distribution Percentage (SPD%) were analyzed throughout, using two pressure mats positioned on seat cushion and backrest. Whole-body and local discomfort for each body part were rated every 20 min. The softer seat, S-1, induced a greater contact surface on cushion and backrest and a lower SPD%, reflecting better pressure distribution. Pressure profiles were asymmetrical for both S-1 and S-2, with higher CP under left buttock (LBu) and right lower back (RLb) and greater CS under thighs and RLb. Pressure distribution was less homogeneous on mountain and city roads than on monotonous roads (highway and country). Despite the pressure differences between the seats, however, both led to similar increases in perceived whole-body discomfort throughout the driving session. Moreover, the highest discomfort scores were in the neck and the lower back areas, whatever the seat. These findings on pressure variables may have implications for the design of backrests and cushions to ensure more homogeneous pressure distribution, even though this is not shown to minimize perceived driver discomfort.