Compañía Minera del Pacífico (CMP) is the main iron producer on the Pacific coast of the American continent. The Cerro Negro Norte (CNN) operation of CMP is facing important challenges, such as the processing of low-grade ores containing complex gangue minerals which negatively affect the performance of the magnetic separation, grinding and solid–liquid separation stages. CMP is working on a program, aimed at optimizing the efficiency of the CNN plant, which considers a rheological characterization of the slurries produced by the different ores treated, information which will be useful to optimize the performance of the physical separation processes. The objective of this work was to characterize the slurries obtained from the secondary grinding and tailings thickener stages through rheological measurements. The rheological data were correlated with the physical, chemical and mineralogical characteristics of the different geological units (GU) tested. The results show that the rheological flow curves of the slurries taken from the secondary grinding product display a pseudoplastic behavior which follows a Casson model pattern. An exponential model was used to correlate the Casson yield stresses with the solids content of the slurries taken from the secondary grinding product. The results of this fitting process indicate that the yield stresses increase with the % −325# Tyler mesh and with the percentage of minerals with a tendency to generate fines (MTF = smectite + illite/mica + talc + chlorite + kaolinite), and in contrast the yield stresses decrease with the ore iron grade (Fe). For the tailings characterization, the results of settling rates and turbidity values of the supernatant obtained from tests with different GU samples show no significant differences. A linear regression model was used to correlate the results of yield stresses of compacted tailings with the chemical and mineralogical characteristics of the GU. The results of the fitting process indicate that the MTF content in the head ore samples influence the rheological properties of the tailings, which correlates with the behavior of the secondary grinding product. The increase in the GU iron grades also reduced the Casson yield stress. The experimental results were explained in terms of the microrheological effects and the physicochemical properties of the different types of phyllosilicates existing in the ore samples tested in this work.