This study provides an in-depth analysis of the hydrochemical characteristics and their controlling factors in the lower reaches of the Yellow River. Through water quality sampling and analysis over two hydrological periods within a year, combined with hydrochemical methods and machine learning techniques, the study reveals the joint impact of natural factors and human activities on the spatiotemporal variations in hydrochemical constituents. The findings indicate that the water in the lower reaches of the Yellow River exhibits weak alkalinity (the pH is between 7 and 8), with the primary hydrochemical type being HCO3·SO4—Ca·Na·Mg. The temporal variation in the hydrochemical constituents is mainly influenced by rainfall, where nitrate levels are higher during the flood season due to the flushing effect of rainfall, whereas other hydrochemical constituents show an opposite temporal pattern due to the dilution effect of rainfall. The spatial variation in the Yellow River’s hydrochemistry is primarily controlled by a combination of human activities and rainfall. Using Gibbs diagram analysis, it is identified that rock weathering is the main source of ionic constituents, while agricultural fertilization, industrial emissions, and domestic wastewater discharge have significant impacts on the hydrochemical constituents. Compared to other rivers worldwide, the concentration of hydrochemical constituents in the lower reaches of the Yellow River is relatively high, especially nitrate and sulfate, which is closely related to the geological characteristics of the Yellow River basin and intense human activities in the middle and lower reaches. Principal component analysis reveals that the main controlling factors for hydrochemical constituents during the dry season in the lower reaches of the Yellow River are rock weathering dissolution and industrial activities, followed by domestic wastewater; during the flood season, the main controlling factors are rock weathering dissolution and industrial activities, followed by agricultural activities and domestic wastewater. The research findings provide theoretical support for water resource management and water quality protection in the lower reaches of the Yellow River.