Rock shear strength plays a fundamental role in volcano flank collapse, yet pertinent data from modern collapse surfaces are rare. Using samples collected from the inferred failure surface of the massive 1980 collapse of Mount St. Helens (MSH), we determined rock shear strength via laboratory tests designed to mimic conditions in the pre-collapse edifice. We observed that the 1980 failure shear surfaces formed primarily in pervasively shattered older dome rocks; failure was not localized in sloping volcanic strata or in weak, hydrothermally altered rocks. Our test results show that rock shear strength under large confining stresses is reduced ∼20% as a result of large quasi-static shear strain, as preceded the 1980 collapse of MSH. Using quasi-3D slope-stability modeling, we demonstrate that this mechanical weakening could have provoked edifice collapse, even in the absence of transiently elevated pore-fluid pressures or earthquake ground shaking. Progressive strength reduction could promote collapses at other volcanic edifices.