Optimizing hydrocarbon production and waste management from unconventional oil and gas extraction requires an understanding of the fluid-rock chemical interactions. These reactions can affect flow pathways within fractured shale and produced water chemistry. Knowledge of these chemical reactions also provides valuable information for planning wastewater treatment strategies. This study focused on characterizing reservoir reactions through analysis of produced water chemistry from the Marcellus Shale Energy and Environmental Laboratory field site in Morgantown, WV, USA. Analysis of fracturing fluids, time-series produced waters (PW) over 16 months of operation of two hydraulically fractured gas wells, and shale rocks from the same well for metal concentrations and multiple isotope signatures (δH and δO of water, δLi, δB, Sr/Sr) showed that the chemical and isotopic composition of early (<10 days) PW samples record water-rock interactions during the fracturing period. Acidic dissolution of carbonate minerals was evidenced by the increase in TOC, B/Na, Sr/Na, Ca/Na, and the decrease in Sr/Sr in PW returning in the first few days toward the Sr/Sr signature of carbonate cement. The enrichment of Li in these early (e.g., day 1) PW samples is most likely a result of desorption of Li from clays and organic matter due to the injection of fracturing fluid. Redox-active trace elements appear to be controlled by oxidation-reduction reactions and potentially reactions involving wellbore steel. Overall, PW chemistry is primarily controlled by mixing between early PW with local in-situ formation water however certain geochemical reactions (e.g., carbonate cement dissolution and desorption of Li from clays and organic matter) can be inferred from PW composition monitored immediately over the first ten days of water return.