The Manas River Basin (MRB), Northwest China, is an arid basin dependent on irrigation for agriculture, and human activities are believed to be the primary factor affecting the groundwater level fluctuations in this basin. Such fluctuations can have a significant adverse impact on the social economy, agricultural development, and natural environment of that region. This raises concerns regarding the sustainability of groundwater use. In this study, we used ArcGIS spatial interpolation and contrast coefficient variance analysis to analyse groundwater level, land-use change, and water resource consumption patterns from 2012 to 2019 in the plains of the MRB. The aim was to determine the main factors influencing the groundwater level and to provide a scientific basis for the rational development, utilisation, and management of water resources in this area. During the study period, the groundwater level decreased, increased, and then fluctuated with a gradually slowing downward trend; the decline ranged from −17.82 to −11.67 m during 2012–2019. Within a given year, groundwater levels declined from March/April to August/September, then rose from August/September to March/April, within a range of 0.29–19.05 m. Primary factors influencing the groundwater level included human activities (e.g., changes in land use, river regulation, irrigation, and groundwater exploitation) and natural causes (e.g., climate and weather anomalies). Human activities were the primary factors affecting groundwater level, especially land-use change and water resource consumption. These results provide a theoretical basis for the rational exploitation of groundwater and the optimisation of water resource management in this region.