It is widely observed that mafic rocks are able to accommodate high strains by viscous flow. Yet, a number of questions concerning the exact nature of the involved deformation mechanisms continue to be debated. In this contribution, rock deformation experiments on four different water-added plagioclase–pyroxene mixtures are presented: (i) plagioclase(An60–70)–clinopyroxene–orthopyroxene, (ii) plagioclase(An60)–diopside, (iii) plagioclase(An60)–enstatite, and (iv) plagioclase(An01)–enstatite. Samples were deformed in general shear at strain rates of 3×10−5 to 3×10−6 s−1, 800 °C, and confining pressure of 1.0 or 1.5 GPa. Results indicate that dissolution–precipitation creep (DPC) and grain boundary sliding (GBS) are the dominant deformation mechanisms and operate simultaneously. Coinciding with sample deformation, syn-kinematic mineral reactions yield abundant nucleation of new grains; the resulting intense grain size reduction is considered crucial for the activity of DPC and GBS. In high strain zones dominated by plagioclase, a weak, nonrandom, and geometrically consistent crystallographic preferred orientation (CPO) is observed. Usually, a CPO is considered a consequence of dislocation creep, but the experiments presented here demonstrate that a CPO can develop during DPC and GBS. This study provides new evidence for the importance of DPC and GBS in mid-crustal shear zones within mafic rocks, which has important implications for understanding and modeling mid-crustal rheology and flow.