In this study, we investigated the distribution and the principal sources of macronutrients (N, P, K, S) in groundwater in agro-pastorally dominated North Cameroon. Graphical methods and multivariate statistics were used to understand the impact of land use and regional geology on nutrient concentrations (K+, NO3−, SO42−, PO43−). Groundwater was acidic (median pH 6.8) and more mineralized (EC range = 35–2500 µS/cm, median = 376 µS/cm) than surface water (EC range = 50–222 µS/cm, median = 81 µS/cm). The median concentration of nutrients was (in mg/L) in the order NO3− (41.3) > SO42− (7.7) > K+ (5.2) > PO43− (0.1) in groundwater and rather K+ (3.3) > NO3− (0.3) > SO42− (0.2) > PO43− (0.2) in surface water. Using hierarchical cluster analysis and Schoeller diagram, we identified three distinct water quality groups. Group I, which contained cluster 1 and 2 were generally less mineralized and characterised as Na + K − HCO3 water type found in the urban area such as Garoua and Lagdo. Group II, containing cluster 3 was much higher mineralized and characterised as the Na + K − HCO3 water type with elevated nitrate. The occurrence of these groups is linked to the outcrops of cretaceous terrestrial sediments of the Garoua basin. Group III, which contained cluster 4 were heavily mineralized and characterised as the Ca + Mg − NO3 water type. The occurrence was controlled by the outcrop of the crystalline Proterozoic basement. The nitrate median (41 mg/L) found in groundwater demonstrates the influence exerted by anthropogenic activities. Management strategies are required for the whole study area to limit further deterioration of groundwater resources in the wake of the planned expansion of agricultural productivity in the North Region of Cameroon.