Explicitly incorporating the effects of chemical phenomena such as chemical pretreatment and mineral scaling during the design of treatment systems is critical; however, the complexity of these phenomena and limitations on data have historically hindered the incorporation of detailed water chemistry into the modeling and optimization of water desalination systems. Thus, while qualitative assessments and experimental studies on chemical pretreatment and scaling are abundant in the literature, very little has been done to assess the technoeconomic implications of different chemical pretreatment alternatives within the context of end-to-end water treatment train optimization. In this work, we begin to address this challenge by exploring the impact of pH control during pretreatment on the cost and operation of a high-recovery desalination train. We compare three pH control methods used in water treatment (H2SO4, HCl, and CO2) and assess their impact on the operation of a desalination plant for brackish water and seawater. Our results show that the impact of the acid choice on the cost can vary widely depending on the water source, with CO2 found to be up to 11% and 49% more expensive than HCl in the seawater and brackish cases, respectively. We also find that the acid chemistry can significantly influence upstream processes, with use of H2SO4 requiring more calcium removal in the softening step to prevent gypsum scaling in HPRO system. Our work highlights why incorporating water chemistry information is critical when evaluating the key cost and operational drivers for high-recovery desalination treatment trains.