Spontaneous microfracture propagation caused by mineral crystallization or growth has been demonstrated in a variety of volume-increasing mineral replacement reactions. This brings a new look on the way microfractures may be generated in the shale formation. Because carbonates and pyrite are highly reactive minerals during shale-fluid reactions and may be the most common sources of replacement reactions, 10 wt % sulfuric acid (H2SO4) and 10 wt % ammonium persulfate ((NH4)2S2O8) solutions were used to react with the centimeter- and millimeter-sized shale samples, which have a reactive mineral composition of 2.2-4.7 wt % calcite (CaCO3) and 4.3-4.8 wt % dolomite (CaMg(CO3)2), and 1.8-2.7 wt % pyrite (FeS2). A deionized water experiment was performed as a replacement-free control. We monitored the reaction-induced fractures using X-ray tomography and scanning electron microscopy imaging. The related mineral dissolution and new mineral precipitation were also examined. Experiments showed that reactions of the unconfined shale samples with H2SO4 and (NH4)2S2O8 solution have a great potential for generating chemically induced fractures, because of the replacement of carbonate minerals by gypsum (CaSO4·2H2O) crystal. The replacement process was supposed to occur via an interface-coupled dissolution-precipitation reaction. It allows the gypsum precipitation in the immediate vicinity of the dissolving carbonate mineral surfaces. Because gypsum has a higher molar volume (74.4 cm3/mol) than calcite (36.9 cm3/mol) and dolomite (64.3 cm3/mol), the local replacement reactions can generate internal swelling stress that drives fracturing of the surrounding shale matrix. The reaction-induced stress is on the grain scale and derived from the crystallization pressure. Based on the calculation from the degree of supersaturation of CaSO4 solution, the crystallization pressure can easily exceed 30 MPa, which may provide a sufficient local swelling stress to cause intensive shale microfracturing. This implies that the replacement of calcite and dolomite grains by calcium sulfate crystals could provide an additional driving force to generate microfractures during shale hydraulic fracturing.