Nitrate contamination of groundwater is a pressing global concern, affecting over 80 million people worldwide, with agricultural activities being the primary contributor to nitrogen inputs into aquifers. The primary objective of this study was to identify the predominant sources of nitrate pollution and biogeochemical transformations in the semiarid region of the Meoqui-Delicias aquifer, Mexico. In this region, the uncontrolled use of chemical fertilizers and manure leads to excessive nutrient input, which accelerates the deterioration of groundwater quality. This study introduces an innovative dual-model approach (δ15NNO3 vs. δ11B) to compare the Bayesian Isotope Mixing Model (BIMM) with Positive Matrix Factorization (PMF) for nuanced source apportionment. This approach enhanced the differentiation between manure and sewage as nitrate sources. Results from the δ15NNO3 vs. δ11B model revealed that manure (52.4%) was the most significant source of nitrate pollution in the aquifer, followed by soil (37.4%), chemical fertilizers (5.5%), and sewage (4.7%). The PMF model corroborated this finding and indicated that 60.2% of the NO3–-N pollution in the aquifer was attributed to manure and sewage, confirming the superior performance of the proposed BIMM in source differentiation. Our findings enhance the understanding of nitrate dynamics in semi-arid regions and can serve as a scientific evidence base for targeted interventions in nutrient management in the study area and elsewhere.