Groundwater chemistry is a crucial component of the groundwater environment. Understanding the basic hydrogeochemical characteristics and their influencing factors is the basis of conducting groundwater quality research. The impact of agricultural activities on the groundwater quality is largely reflected through the changes in hydrochemical compositions. Therefore, studying the formation, distribution, and evolution of groundwater chemistry under the influence of agricultural activities has significant theoretical implications for a profound understanding of the mechanisms by which agricultural activities impact the groundwater environment. This chapter, taking the Weining Plain, which has over 2000 years of irrigation history, as an example, employs hydrogeochemical and isotopic techniques to investigate the formation, distribution, and evolution of groundwater chemistry under the influence of agricultural activities.