There is a need to investigate the role of muscle architecture on muscle damage responses induced by exercise. The aim of this study was to determine the effect of muscle architecture and muscle length on eccentric exercise-induced muscle damage responses. Eccentric exercise-induced muscle damage was performed randomly to the elbow flexor (EF), knee extensor (KE), and knee flexor (KF) muscle groups with two week intervals in 12 sedentary male subjects. Before and after each eccentric exercise (immediately after, on the 1st, 2nd, 3rd, and 7th days) range of motion, delayed onset muscle soreness, creatine kinase activity, myoglobin concentration and isometric peak torque in short and long muscle positions were evaluated. Furthermore, muscle volume and pennation angle of each muscle group was evaluated before initiating the eccentric exercise protocol. Pennation angle and muscle volume was significantly higher and the workload per unit muscle volume was significantly lower in the KE muscles compared with the KF and EF muscles (p < 0.01). EF muscles showed significantly higher pain levels at post-exercise days 1 and 3 compared with the KE (p < 0.01 -0.001) and KF (p < 0.01) muscles. The deficits in range of motion were higher in the EF muscles compared to the KE and KF muscles immediately after (day 0, p < 0.01), day 1 (p < 0.05 -0.01), and day 3 (p < 0.05) evaluations. The EF muscles represented significantly greater increases in CK and Mb levels at day 1, 3, and 7 than the KE muscles (p < 0.05 -0.01). The CK and Mb levels were also significantly higher in the KF muscles compared with the KE muscles (p < 0.05, p < 0.01 respectively). The KF and EF muscles represented higher isometric peak torque deficits in all the post -exercise evaluations at muscle short position (p < 0.05 -0.001) compared with the KE muscle after eccentric exercise. Isometric peak torque deficits in muscle lengthened position was significantly higher in EF in all the post-exercise evaluations compared with the KE muscle (p < 0.05 -0.01). According to the results of this study it can be concluded that muscle structural differences may be one of the responsible factors for the different muscle damage responses following eccentric exercise in various muscle groups.