Fluids are abundant in fault zones and play a crucial role during faulting processes, particularly in fluid-rich subduction zones. Fluid-assisted mineral reactions can produce newly formed hydrous and/or anhydrous minerals, however, their effects on fault behavior remain poorly understood. We conducted shear experiments on plagioclase-pyroxene assemblages under varying fluid compositions at pore pressures (Pp) of 30 MPa and 100 MPa, under an effective normal stress of 200 MPa, at temperatures ranging from 300 °C to 600 °C, and with shear rates from 0.0122 um/s to 1.22 um/s. Detailed microstructural analyses were carried out on the experimental samples to investigate the micro-mechanisms of deformation and possible mineral reactions. Under Pp of 30 MPa, the plagioclase-pyroxene assemblages exhibited typical frictional sliding behavior (unstable slip with strain-hardening). However, at Pp of 100 MPa and temperatures ≥ 500 °C, the plagioclase-pyroxene assemblages displayed unstable slip behavior with pronounced strain weakening. Notably, the fluid compositions had a significant influence on fault behavior and the products of mineral reactions. In pure water fluid, dissolution-precipitation processes involving plagioclase and pyroxene led to the formation of new nano-crystalline plagioclase and pyroxene, which controlled strain weakening at low shear rates of 0.0122 μm/s. In iron-rich fluids, pyroxene reacted to form iron-rich pyroxene, while plagioclase reacted to produce chlorite. In magnesium-rich fluids, pyroxene reacted to produce talc and olivine, and plagioclase reacted to form chlorite. Frictional sliding on the newly formed weak minerals, such as talc and chlorite, provides a plausible mechanism for the brittle-ductile transition of plagioclase-pyroxene assemblage. As an example, our shear experiment on oceanic basalt from IODP Expedition 349 drilling site U1431 demonstrated stick-slip behavior followed by strain weakening, which was attributed to fluid-assist mineral reaction in the basalt. Our findings provide valuable experimental insights into the deformation processes occurring in transform faults within oceanic subduction zones.