Water-based hydraulic fracturing requires high-pressure injection of large quantities of water mixed with chemicals into the subsurface, where fluids contact mineral surfaces. Chemical imbalance between minerals and the injected fluids provides the potential for chemical reactions that may induce physical alterations to the rock. We investigate mineral reactivity during in situ water-rock interaction between unconventional reservoir rocks and hydraulic fracturing fluid. We characterized two unconventional reservoir rocks, a calcareous mudstone (B Bench of the Niobrara Formation) and a calcite-cemented sandstone (Wall Creek Member of the Frontier Formation) of the Powder River Basin, Wyoming, USA, and developed, analyzed, and quantified the aqueous geochemistry of a hydraulic fracturing fluid (HFF). These datasets informed the design of numerical simulations that predict mineral-HFF interactions at in situ conditions over a 31-day timeframe. The two unconventional reservoir rocks have similar mineral assemblages, albeit in different proportions, which leads to similar dissolution/precipitation reactions. Calcite, feldspar, and authigenic clay minerals begin to dissolve, and secondary calcite, anhydrite, and illite form. Calcite dissolution increases porosity of the B Bench from 2% to 2.9% and porosity of the Wall Creek from 5% to 5.8%. Mineral-fluid reactions manifest in flowback fluids as temporal geochemical trends consistent with limited field data.