Groundwater is a crucial water resource, particularly in regions with intensive agriculture and a semi-arid climate, such as Campo de Cartagena (Murcia, Spain). Groundwater salinity in the area can be attributed to hydrogeological characteristics, irrigation return water, or even marine intrusion and communication between aquifers. The management of these waters is essential to maintain sustainable agriculture in the area. Therefore, two groundwater salinity prediction models were developed, a backpropagation artificial neural network (ANN) model and a multiple linear regression (MLR) model, based on EC (electrical conductivity) data obtained from official information sources. The data used were the bicarbonate, calcium, chloride, magnesium, nitrate, potassium, sodium, and sulphate concentrations, as well as EC, pH, and temperature, of 495 water samples from 38 sampling stations between 2000 and 2023. Variables with the least influence on the model were discarded in a previous statistical analysis. Based on seven evaluation metrics (RMSE, MAE, R2, MPE, MBE, SSE, and AARD), the ANN model showed a sligntly better accuracy in predicting EC compared to the MLR model. As a result, the ANN model, together with crop tolerance to EC, may be an effective tool for groundwater irrigation management in these areas.