In this study, FLUENT software was used to simulate the flow regime of an integrated sludge thickening and digestion reactor. To optimize the flow regime, the combinational effect of key parameters of the reactor structure was investigated with an L16 (4(5)) orthogonal test. The reactor was then redesigned based on the optimization results, and a series of experiments was conducted to study the treatment effect with sludge dosage rates of 12, 18, 24, and 30%. The operation results showed that the reactor obtained the best treatment efficiency when the sludge dosage rate was 24%. At this dosage, the water content of the sludge decreased from 99.1% to 91.8%, with organic matter content (volatile solids [VS]/total solids) decreasing to 21.2% and average gas production (CH4 62.66%, CO2 11.56%, N2 23.91%, O2 1.59%) reaching 231.3 L/kg VS. Therefore, the results implied that the optimized reactor has good effects on sludge thickening and digestion.