Abstract: Cemented paste backfill (CPB) is a key technology for green mining in metal mines, in which tailings thickening comprises the primary link of CPB technology. However, difficult flocculation and substandard concentrations of thickened tailings often occur. The rheological properties and concentration evolution in the thickened tailings remain unclear. Moreover, traditional indoor thickening experiments have yet to quantitatively characterize their rheological properties. An experiment of flocculation condition optimization based on the Box–Behnken design (BBD) was performed in the study, and the two response values were investigated: concentration and the mean weighted chord length (MWCL) of flocs. Thus, optimal flocculation conditions were obtained. In addition, the rheological properties and concentration evolution of different flocculant dosages and ultrafine tailing contents under shear, compression, and compression–shear coupling experimental conditions were tested and compared. The results show that the shear yield stress under compression and compression–shear coupling increases with the growth of compressive yield stress, while the shear yield stress increases slightly under shear. The order of shear yield stress from low to high under different thickening conditions is shear, compression, and compression–shear coupling. Under compression and compression–shear coupling, the concentration first rapidly increases with the growth of compressive yield stress and then slowly increases, while concentration increases slightly under shear. The order of concentration from low to high under different thickening conditions is shear, compression, and compression–shear coupling. Finally, the evolution mechanism of the flocs and drainage channels during the thickening of the thickened tailings under different experimental conditions was revealed.