Dwindling water resources have drawn global attention to the reuse of treated wastewater (TWW) for irrigation. However, the impact of continuous TWW applications on soil quality and the proper quantification and monitoring frameworks have not been well-understood. This study aims to provides an insight into the impact of flood irrigation of urban TWW on soil nutritional-chemical attributes and the potential application of multiple soil quality indices for a corn cropping system. To achieve that goal, we pursued the Total Data Set (TDS) and Minimum Data Set (MDS) approaches, as well as the Integrated Quality Index (IQI) and Nemoro Quality Index (NQI) models. A total of 17 soil nutritional-chemical indicators (0–50 cm depths) were determined for the soils irrigated with TWW (five sites) and well water (one site as control) in West Azerbaijan province in northwestern Iran. Results revealed a significant difference in the majority of soil nutritional-chemical attributes, IQI-TDS, NQI-TDS, IQI-MDS, NQI-MDS, and corn yield between the TWW-irrigated and well-irrigated soils. Irrigation with TWW resulted in a significant increase in the amount of organic matter and cation exchange capacity by 9–17% and 17–26%, respectively, macronutrients (N, P, K, Ca, and Mg) by 22–164%, and the majority of trace metals (Fe, Mn, Zn, and Cu) by 17–175%, suggesting an improvement in soil nutrients and an increase in productivity. Comparing to the soil in control sites, the TWW irrigation caused a notable increase in the values of IQI-TDS, NQI-TDS, IQI-MDS, and NQI-MDS models ranging 14.6–29.5%, 19.1–25.5%, 21.7–33.3%, and 18.4–23.7%, respectively. This implies that soil quality was ameliorated to a significant extent with TWW irrigation. These improvements resulted in a remarkable increase in corn yield ranging from 12.5% to 28.1%. The regression equations revealed that up to 78%, 47%, 72%, and 36% of the variance in the IQI-TDS, NQI-TDS, IQI-MDS, and NQI-MDS models, respectively, could be captured by corn yield. The results of the regression and correlation analyses showed that the IQI-MDS model was more accurate than the other models in assessing soil quality and predicting crop yield. These findings may be an effective and practical tool for policy making, implementation, and management of soil irrigated with TWW.