Mechanical stimuli increase skeletal muscle growth in a mammalian target of rapamycin (mTOR)- and p70^S6K-dependent manner. It has been proposed that costameric proteins at Z bands may sense and transfer tension to these initiators of protein translation, but few candidates have been identified. The purpose of this study was to determine whether a role exists for the α₇-integrin in the activation of hypertrophic signaling and growth following eccentric exercise training. Five-week-old, wild-type (WT) and α₇BX2-integrin transgenic (α₇Tg) mice were randomly assigned to one of two groups: 1) sedentary (SED), or 2) exercise training (EX). Exercise training consisted of downhill running 3 sessions/wk for 4 wk (−20°, 17 m/min, 30 min). Downhill running was used to induce physiological mechanical strain. Twenty-four hours following the final training session, maximal isometric hindlimb plantar flexor force was measured. Gastrocnemius-soleus complexes were collected for further analysis of signaling changes, which included AKT, mTOR and p70^S6K, and muscle growth. Despite increased p70^S6K activity in WT/EX, no significant changes in cross-sectional area or force were observed in WT/EX compared with WT/SED. AKT, mTOR, and p70^S6K activation was higher, and whole muscle hypertrophy, relative muscle weight, myofibrillar protein, and force were significantly elevated in α₇Tg/EX compared with α₇Tg/SED. A marked increase in average myofiber cross-sectional area was observed in α₇Tg/EX compared with all groups. Our findings demonstrate that the α₇β₁-integrin sensitizes skeletal muscle to mechanical strain and subsequent growth. Thus the α₇β₁-integrin may represent a novel molecular therapy for the treatment of disuse muscle atrophy.