Prolonged driving under real conditions can entail discomfort linked to driving posture, seat design features, and road properties like whole-body vibrations (WBV). This study evaluated the effect of three different seats (S 1 = soft; S 2 = firm; S 3 = soft with suspension system) on driver’s sitting behavior and perceived discomfort on different road types in real driving conditions. Twenty-one participants drove the same 195 km itinerary alternating highway, city, country, and mountain segments. Throughout the driving sessions, Contact Pressure (CP), Contact Surface (CS), Seat Pressure Distribution Percentage (SPD%) and Repositioning Movements (RM) were recorded via two pressure mats installed on seat cushion and backrest. Moreover every 20 minutes, participants rated their whole-body and local discomfort. While the same increase in whole-body discomfort with driving time was observed for all three seats, S 3 limited local perceived discomfort, especially in buttocks, thighs, neck, and upper back. The pressure profiles of the three seats were similar for CP, CS and RM on the backrest but differed on the seat cushion. The soft seats (S 1 & S 3 ) showed better pressure distribution, with lower SPD% than the firm seat (S 2 ). All three showed highest CP and CS under the thighs. Road type also affected both CP and CS of all three seats, with significant differences appearing between early city, highway and country segments. In the light of these results, automotive manufacturers could enhance seat design for reduced driver discomfort by combining a soft seat cushion to reduce pressure peaks, a firm backrest to support the trunk, and a suspension system to minimize vibrations.