Hydraulic fracturing (HF, a.k.a. fracking) is a method of unconventional oil and gas extraction that has allowed the United States to become a leader in natural gas production. However, HF operations generate large quantities of flowback and produced waters (FPW) that require proper disposal. FPWs are wastewaters that contain a complex mixture of chemical additives, salts, and other unknown chemicals. Many chemical additives are semi-polar to polar organic chemicals that can be transported in water resources and are potentially toxic to aquatic life or other organisms. To minimize the risks that chemical additives pose to the environment and human health, it is critical that researchers understand the chemical composition of FPWs and the persistence of chemical additives during the wastewater treatment process to prevent the release of harmful chemicals into the environment. Assessing the organic chemical composition of FPWs and the persistence of organic chemicals in wastewater treatment is complicated by many factors. For example, conventional methods of analysis are focused on the detection or assessment of a single chemical or a small class of chemicals, but over one thousand chemicals have been disclosed as HF additives and many others are undisclosed or unanticipated. FPWs are produced for years after HF operations are completed and it is unclear how the organic chemical composition changes over time. Furthermore, the high levels of salts in FPWs alter the detection and quantification of organic chemicals in FPWs. Screening methods capable of detecting and assessing the persistence of a wide range of chemicals are required to determine the composition of FPWs and identify proper methods of disposal. The overarching goals of this dissertation were to: (1) characterize the semi-polar to polar organic composition of FPWs and develop a method to quantify additives used in HF fluids; (2) characterize the temporal abundance trends of known and unknown constituents within FPWs over more than two years of well production; and (3) assess persistence of organic chemicals in wastewater treatment using an emerging chemical benchmarking approach. I designed three research projects to meet these goals. First, I adapted a broad liquid chromatography high-resolution mass spectrometry (LC-HRMS) method to qualitatively detect and quantify known HF additives in makeup water, hydraulic fracturing fluid, and FPWs from the first six weeks in the life cycle of two natural gas wells in Morgantown, West Virginia. Second, I used this LC-HRMS method and a non-target screening method to examine how FPW composition changed over two years of the same wells’ life cycle and to identify undisclosed additives. Finally, I used chemical benchmarking to examine the persistence of organic chemicals during wastewater treatment and to develop criteria for adopting chemical benchmarking for assessing organic chemical persistence in FPWs. The results of this research contribute to our understanding of the chemical composition of FPWs and offer water quality managers and policy makers essential data to inform the management of FPWs over the life cycle of a natural gas well.