Skeletal muscle responses to exercise depend on contraction mode, which alters the balance between perfusion, oxygenation, and metabolic demand. However, how these physiological responses differ across muscles remains unclear. This study investigated contraction mode-dependent MRI responses in lower-leg muscles using quantitative T2*, T2, and T2′ measurements. Nineteen healthy female participants performed isometric and isotonic plantar flexion in a randomized crossover design. MRI measurements were obtained during inter-set rest periods and the post-exercise recovery phase in the medial gastrocnemius (MG), lateral gastrocnemius, soleus, and tibialis anterior. Time-course changes were analyzed using linear mixed-effects models, and response magnitude was quantified using peak and area under the curve (AUC). Isotonic contraction produced significantly greater T2* responses than isometric contraction, particularly in the medial gastrocnemius (MG), during exercise and early recovery (all false discovery rate-corrected p ≤ 0.027). T2 also showed smaller differences in MG at selected recovery time points, whereas no significant differences were observed in other muscles. Linear mixed-effects models revealed a main effect of contraction mode, and peak and AUC analyses demonstrated that both the magnitude and persistence of responses were greatest in MG. In contrast, T2′ did not show contraction mode differences. Contraction mode influences muscle responses in a muscle-specific manner, with MG showing the greatest sensitivity. The greater sensitivity of T2* may reflect its responsiveness to the combined effects of hemoglobin oxygenation-related susceptibility, microvascular blood volume, and water-related tissue changes. These findings provide insight into muscle-specific MRI responses and may inform the optimization of rehabilitation strategies.