In order to study the mutual effect of deformation and mineral reactions, we have conducted shear experiments on fine-grained plagioclase-pyroxene assemblages in a Griggs-type solid-medium deformation apparatus. Experiments were performed at a constant shear strain rate of 10−5 s−1, a confining pressure of 1 GPa and temperatures of 800, 850 and 900 °C. While the peak stress of plagioclase + orthopyroxene assemblages reaches values between those of the end-member phases, the strength of polymineralic materials strongly decreases after peak stress and reaches flow stresses that stabilize far below those of the weaker phase (plagioclase). This weakening correlates with the coeval development of high-strain shear zones where new phases are preferentially produced, including new pyroxene, plagioclase and amphibole. The reaction products mostly occur as intimately mixed phases within fine-grained and interconnected shear bands, together with different compositions with respect to the starting material. This indicates that deformation significantly enhances the kinetics of mineral reactions, which in turn strongly weaken the deforming sample, here attributed to a switch to grain-size-sensitive diffusion creep through phase nucleation and grain size reduction. Such an interplay between deformation and mineral reactions may have strong implications for the initiation, development, and durability of shear zones in the lower crust.