The interaction between gastrocnemius medialis (GM) muscle and Achilles tendon, i.e., muscle-tendon unit (MTU) interaction, plays an important role in minimizing the metabolic cost of running. Foot-strike pattern (FSP) has been suggested to alter MTU interaction and subsequently the metabolic cost of running. However, metabolic data from experimental studies on FSP are inconsistent, and a comparison of MTU interaction between FSP is still lacking. We, therefore, investigated the effect of habitual rearfoot and mid-/forefoot striking on MTU interaction, ankle joint work, and plantar flexor muscle force production while running at 10 and 14 km/h. GM muscle fascicles of 9 rearfoot and 10 mid-/forefoot strikers were tracked using dynamic ultrasonography during treadmill running. We collected kinetic and kinematic data and used musculoskeletal models to determine joint angles and calculate MTU lengths. In addition, we used dynamic optimization to assess plantar flexor muscle forces. During ground contact, GM fascicle shortening ( P = 0.02) and average contraction velocity ( P = 0.01) were 40–45% greater in rearfoot strikers than mid-/forefoot strikers. Differences in contraction velocity were especially prominent during early ground contact. Moreover, GM ( P = 0.02) muscle force was greater during early ground contact in mid-/forefoot strikers than rearfoot strikers. Interestingly, we did not find differences in stretch or recoil of the series elastic element between FSP. Our results suggest that, for the GM, the reduced muscle energy cost associated with lower fascicle contraction velocity in mid-/forefoot strikers may be counteracted by greater muscle forces during early ground contact. NEW & NOTEWORTHY Kinetic and kinematic differences between foot-strike patterns during running imply (not previously reported) altered muscle-tendon interaction. Here, we studied muscle-tendon interaction using ultrasonography. We found greater fascicle contraction velocities and lower muscle forces in rearfoot compared with mid-/forefoot strikers. Our results suggest that the higher metabolic energy demand due to greater fascicle contraction velocities might offset the lower metabolic energy demand due to lower muscle forces in rearfoot compared with mid-/forefoot strikers.